The first episode is a rather faithful interpretation of the first issue of the comic book. The main differences are (1) the opening with the little girl zombie, (2) an extended scene before Rick gets shot, (3) the show containing more background on Morgan and Duane Jones and (4) the comic not showing us the fate of Lori until the next issue and while also not featuring Morgan's wife and Duane's mother, Jenny. The remaining episodes of the first season diverge fairly widely in terms of plot. The general idea of the camp outside of Atlanta is the same and most of the characters in the camp are in the comic.
In the comic, it is Glenn alone who rescues Rick rather than a group. In the comic, they only make a trip back into Atlanta to get supplies and guns. The Dixon brothers, the extended zombie siege of the department store, and the Vatos were all invented for the show. In addition in the comic, Shane dies before they break camp, and there is no CDC subplot. The TV show adds several characters such as the Dixon brothers, T-Dog, Ed Peletier (who was said to be dead before the events of the comics), Jacqui and the Morales family (though they could be the counterparts to Allen & Donna's family that consists of four members).
It also makes some changes to existing characters. For example, in the comics Lori and Shane do not have an ongoing romantic relationship but rather have a furtive, one-night stand outside of Atlanta. Carol seems younger in the comics than in the show. Also, Andrea is significantly younger in the comics, being in her mid twenties and relatively fresh out of college. In contrast to the show, the comic shows Andrea being a naturally gifted shooter who quickly becomes one of the group's top zombie killers.
The second season also diverges from the books. The idea of Carl being accidentally shot by Otis and taken to Hershel's barn is the same though Otis in the comics shot Carl as he believed he was a zombie whereas the TV series Otis accidentally shot him in a hunting accident. However, the show spends much more extensive time at Hershel's farm than the books do. In the books, there is no zombie attack on the road or the farm. Also the zombie herds were introduced much later in the comic series, and Sophia does not go missing and end up as a zombie. In the books, Hershel's family is bigger, consisting of seven kids, although several of the characters are barely developed. Only two of Hershel's children from the comics appear though Shawn Greene was Hershel's oldest and biological child. He's younger than Maggie and is Hershel's step-son in the series.
In the books, Hershel is rather less standoffish than he is on the show, where he's much kinder and calmer, and allows Rick's group to stay, whereas he kicks them out in the comics. The fact that the barn contains penned up zombies is revealed very early in the group's stay as Hershel had no reason to keep it a secret in the comics while, in the show, Hershel's family keeps it secret for much of the season. Rick in the comics wanted to put down the barn zombies while in the series he cooperated with Hershel to pen them up in the barn.
In the show, Otis is depicted as an overweight man and is killed by Shane while trying to get medical supplies for Carl. In the comics, Otis is depicted as being of average build. While generally good-natured, the comic version of Otis is less heroic than the show version and is also a racially bigoted. The comic version of Otis lives longer than on the TV show, same with Patricia who was Otis's girlfriend in the books where their relationship is not so strong, whereas they have a strong marriage in the TV series. The comic lacks the subplot about Randall and a group of attackers as well as the conflict over what to do with them. In the comics, it was Carl that killed Shane when he attempted to kill Rick who then put down his zombified form back in the Atlanta camp. In the show, Rick & Carl's roles were reversed, and Lori was upset about Shane's death while her reaction was the opposite in the comics. In contrast, Rick never killed a living survivor before the events of the prison whereas he killed three in the series.
Perhaps the biggest change from the comics is the fate of Dale. In the show, he is killed by a zombie. In the books, he lived much longer, also, by the time they reach Hershel's farm in the comics, Dale and Andrea have already begun a sexual relationship. During the end of the farm, Hershel and his remaining kids join Rick's group on his journey. In the comics, he decided to stay at his farm, only joining Rick's group later on. And lastly, it was Otis who Michonne saved to join the group whereas it's Andrea in the TV series though Michonne was introduced earlier, right after the farm event, whereas her comic counterpart's was introduced a couple of weeks after the group finds the prison, also noting, Andrea never gets separated from her group and is the one that finds the prison in the comics. In the comics, Rick finds out at the prison that everyone is infected. In the TV series, he knew before the farm events.
The third seasons strays further away from the comics, the group finding the prison just a day or two, whereas it took them eight months to find in the series. The prison also consisted of four inmate survivors instead of five: Axel and Andrew are the only two of four Prisoners to be introduced from the comics though Andrew is more confident than his comic counterpart. None of the Prisoners in the comics attempted to kill Rick while two of the inmates in the series did try to kill him. The leader of the Prisoners was a lot more welcoming than the one in the series. The Prisoners were killed much quickly in the TV series which also consists of the idea of one of the inmates, Andrew, killing two members of Rick's group, as the TV series inmate caused the deaths due to revenge while the comic inmate was an obsessed serial killer who pretended to be a harmless tax evader but was actually one who targets women and beheads them. The victims of the outcomes are different.
Lori Grimes died much earlier in the series. In the comics, she was killed by a Woodbury guard along with Judith in the final battle of the Woodbury-Prison arc. The hallucinating phone conversation Rick has with Lori occurs but it is only her that Rick talks to in the comics. The TV series has Rick speaking to Amy, Jim and Jacqui before speaking with his deceased wife, the conversations taking place in the prison whilst it occurred after the Prison arc in the comic.
The television version of the Governor is significantly more handsome than in the comic book. In the comics, he has long stringy hair and a mustache. On the show, it is Andrea and Michonne who encounter the Governor and are taken back to Woodbury. In the comic, it is Glenn, Rick and Michonne who stumble upon Woodbury while looking for a crashed helicopter (which was a news helicopter instead of a National Guard one). Andrea never meets the Governor, but only sees him from a distance. In contrast to the show, where the Governor maintains an air of cautious friendship; in the comic, he quickly establishes himself as hostile to Rick's group and cuts off Rick's hand and brutally tortures and rapes Michonne. Only one inmate (Axel) in the comics gains the groups trust while in TV series, two inmates (Oscar and Axel) gain the groups trust and officially joins them. Caesar Martinez appears to be the only supporting character from Woodbury to appear from the comics. He also plays a bigger role than his comic counterpart. In the TV series, he is one of the Governor's lieutenants, while his relationship with the Governor is unknown in the comics as they only interacted off panel. It is also worth noting that Martinez wore a bandanna in the comics rather than a baseball hat.
The comic book Governor kills any survivor upon meeting them and has them chopped up and fed to the arena zombies unless they have something that is of value to him. The TV Governor welcomed Andrea and Michonne to Woodbury. Dr. Stevens plays an important role in the comics and is a Caucasian man. For the series, his character was changed to an Black woman with a minor role. The Governor doesn't know the whereabouts of the prison, while his TV counterpart knows the exact location and wants to destroy the prison, whereas his comic counterpart wants to take over it.
Also in the comics, the arena zombies including Penny never had their teeth and nails taken out for protection, and it only occurs once where the Governor takes teeth out of Penny after being mutilated by Michonne. The confrontation between Michonne and the Governor plays out differently in the comics: he doesn't put up a fight but rather he was tied up and in addition to losing his eye where it was pulled out instead of being stabbed, he also loses an arm and private parts in the process. Penny is spared, while in the TV series she is killed by Michonne. In the comics, there was no attack on Woodbury for a rescue mission.
In the comics, Tyreese was introduced before Hershel's farm with his daughter and her boyfriend, whereas he was introduced later on in the TV series with his sister and Allen, Donna and Ben. Allen and Donna were part of Rick's Atlanta group in the comics where Allen was a lot nicer and friendly to others and was also good friends with Rick. Allen & Donna's deaths occurred before the Governor's introduction, however, in the TV series, they died after the Governor was introduced. Ben in the comics had a twin and was younger than Carl.
Morgan Jones was also brought back much earlier: Rick returns to his home town to find him after the prison siege in the comic series (in which Morgan decided to join him while he declined in the series). Axel was killed midway in the Prison arc while he dies in the final stage in the comics, his death is the same but his killer is different.
Rick's group suffered the most casualties in the comics, forcing him and the remaining survivors to flee the prison, while the Governor suffers the most casualties in the series. In the comics, the Governor never turns on and kills his own people but one of his people turns on him and kills him in the comics. The Woodbury residents do not join Rick's group in the comics, but rather their fates were left unknown after the prison siege. The biggest change was the death of Andrea who is currently alive in the comics along with Sophia.
In addition, the Governor's identity is more specific. In the first of the novel series which tells his story, his real name is Brian Blake who was actually Penny's uncle, a weak cowardly loser, and Philip was his successful younger brother who was a headstrong leader with anger issues who was killed in the apocalypse by his best friend after Philip began murdering people to feed his zombified daughter Penny human flesh, between which, Brian was blamed and beaten by Philip for failing to protect her. After avenging his brother's death, he took on Philip's personality traits along with his name and seems to even take on Philip's personality. It is safe to assume he also adopted his brother's insanity during his role as the Governor. In the show, the Governor tells Andrea that his name is Phillip, which may or may not be true, and in general is known to be Penny's father, which does seem to be true. In the subsequent season, he goes by the name of Brian to another group of people. The Governor utters his real name once in the comics while pulling out his zombified nieces teeth.
The character of Bob Stookey was a local Woodbury resident who was an alcoholic that was a good friend of the Governor. In the series, however, he is just a survivor with no definite connection to Woodbury or the Governor and also seems to be a recovering alcoholic. The series has changed his age and ethnicity, as Stookey in the comics is an elderly Caucasian man while the series has him as a young Black man. The idea of an illness occurring and killing survivors has also been invented for the show as the comics haven't explored that concept. Rick and Tyreese do engage in a fist fight but it is Tyreese who ends it, savagely beating Rick to a pulp. In the TV series, it is the opposite: with Rick only knocking down Tyreese after one punch. Carol in the comics has never killed while her TV counterpart killed numerous counts of zombies and two people in cold blood.
The Chamblers family (who are the TV counterparts of the Chalmers family) only appear in the first novel series, Rise of the Governor, which tells the story of the Governor in the early days of the apocalypse and how he came to be before encountering Rick Grimes and his group. The novel only consisted of three members of the family: David Chalmers (father), and Tara and April Chalmers (daughters). The TV series, however, only features David and Tara, April's name having been changed to Lilly. In the comics, a character named Lilly was a Woodbury resident who plays a vital role and is the main character in the second novel series titled Road to Woodbury, and there was no Meghan Chalmers though there was a Megan Lafferty who appeared in the second novel where she's good friends with Lilly and is an adult. Tara was the eldest of the two sisters in the novel, whereas in the TV series, she's the youngest. Also, Tara held a grudge towards the Governor (going by the name of Phillip) after he kills her zombified father in the novel while in the series she understood and was okay with the Governor (going solely by the name of Brian) after killing her zombified father. In addition, the Governor never gets romantically involved with April but rather it was his brother who does (and winds up raping her during their encounter) which resulted in Tara throwing them out; and the remaining Chalmers sisters never returned in future storylines after throwing out the Governor and his group.
In the show, Caesar Martinez's death plays out differently than his comic counterpart's who died before Woodbury's first attack on the prison in the comics as he was killed by Rick Grimes; as Rick believed Martinez betrayed his trust, after Martinez helps him, Michonne and Glenn escape from Woodbury, only to run off back to Woodbury after learning the location of the prison to inform the Governor of their location, while claiming that he went back to bring the good Woodbury people to the prison, possibly legitimately as his relationship with the Governor was never explored. The Governor and Woodbury were already in possession of a tank. In the TV series, the Governor joins a group who are in possession of one.
The final assault upon the prison is played out in a similar manner but with different events. It was Tyreese who was captured when he and Michonne went out to hunt down the Governor after the first assault. Tyreese was decapitated in the Governor's second attack upon the prison. Unlike the TV series, comic book Michonne was never present when the decapitation took place as she was never captured and thus never present in the final attack upon the prison. Hershel Greene is killed by the Governor in the comics but with shot to the head, whereas in the TV series, he takes comic book Tyreese's place and was decapitated in the final prison battle with Michonne present, as they had both been captured during a supply run instead of due to a failed assassination attempt as in the comics. Maggie and Glenn were never present in the second and third battles, as they had retreated back to Hershel's farm after the first attack. In the series, however, they were both present. Rick never engaged the Governor in a melee brawl in the comics, as the Governor was smaller and weaker.
The Governor's death plays out differently in the comics. He is killed by Lilly Caul (the main character in Road to Woodbury) after she guns down Lori Grimes, only to find out she also killed Judith Grimes, and comes to the realization that he was bad and in turn kills him by shooting him in the head after the remaining prison survivors escaped. In the series, Lilly Chambler shoots him in the head to put him out of his misery after Michonne stabs him in the chest. In addition, only Rick and Carl survived the final attack and are joined later by Michonne who went to the prison to find any remaining prison survivors and ended up putting down a zombified Tyreese's head after escaping the Governor's clutches. In the TV series, Michonne was with Rick and Carl only to breakaway from them. In addition Rick only suffered two casualties resulting from the Governor's attack. Also, not all of the Governor's people (who had no military training) were killed in the comics, the remaining being led to the prison by Lilly Caul after his demise. The third novel, The Fall of the Governor, tells what happened to Lilly and her group. In the TV show, all the Governor's people (who did have military training) were killed, only Lilly and Tara surviving the battle. In the show, the prison survivors split up into five groups. In the comics, it is only two groups after the attack.
Michonne's back story is similar to her comic counterpart with a few differences. Mike was not her husband but her boyfriend, and Michonne had two daughters and no son from a previous marriage though her daughter whereabouts are unknown and Mike's friend, Terry, was a Caucasian.
Among other things, the journey from the state of Georgia to the state of Virginia is depicted in the show.
In the comic books, Abraham is the one shot with a crossbow by Dwight, and Eugene was present. On the show, they put Denise in his place, and Daryl and Rosita were with her, while Eugene was already Dwight's hostage. It's the same method of death, being shot in the back of the head and fighting to finish a sentence with a lack of pain before dying.
The man that introduced Rick's group to the Hilltop is Paul Monroe, not Paul Rovia.
In the comic books, only Glenn was killed by Negan during their first encounter with him. Abraham was already dead before then.