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 contains more background on Morgan and Duane Jones and 4) the comic does not show us the fate of Lori until the next issue and also does not feature Morgan's wife & 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 20s 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.
Season two 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 herd 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 7 kids, although several of the characters are barely developed, only 2 of Hershel's children from the comics appear though Shawn Greene was Hershel's oldest & biological child, he's younger than Maggie and is Hershel's step-son in the series.
In the books Hershel is rather less stand-offish 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 racist. 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 3 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. Rick finds out at the prison that everyone is infected, the TV series, he knew before the farm events.
Season 3 strays further away from the comics, the group finds the prison just a day or two whereas it took them 8 months to find in the series. The Prison also consisted of 4 inmate survivors instead of 5, only Axel & Andrew are the only 2 of 4 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 tried 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 series, the TV series also consist of the idea of one of the inmates killing two members of Rick's group, 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 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 soldier 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 Rick talks to in the comics, the TV series has Rick speaking to Amy, Jim & Jacqui before speaking with his deceased wife, the conversation took 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 Military 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 & Axel) gains 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 bandana in the comics rather than a baseball hat.
Comic 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, TV Governor welcomed Andrea & Michonne to Woodbury. Dr Stevens plays an important role in the comics and was a male Caucasian, his character was changed to an African-American female with a minor role. The Governor doesn't know the whereabouts of the Prison while his TV counterparts knows the exact location, also The Governor 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, it only occurs once where The Governor only takes teeth out of Penny after being Mutilated by Michonne. The confrontation between Michonne and The Governor plays out differently in the comics, The Governor 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 was killed by Michonne, also noting that 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, he was introduced later on in the TV series with his sister and Allen, Donna & Ben. Allen & 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 and 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, he never turns on and kills his own people but one of his people turns on him and kills him in the comics. And the Woodbury residents do not join Rick's group in the comics, 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 different, In the first of the novel series which tells his story, his real name is Brian Blake who was actually Penny's uncle, he was a weak cowardly loser and Philip was his successful younger brother who was a headstrong leader with anger issues that was killed in the apocalypse by his best friend after Philip began murdering people to feed his zombified daughter Penny human flesh in which Brian was blamed and beaten by Philip for failing to protect her. After avenging his brothers 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. What the show did was make the real Philip the Governor and cut out Brian's identity, it's assumed that Brian Blake doesn't exist in the series. 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 connection to Woodbury or The Governor and also seems to be a recovering alcoholic. Also, the series has changed his age and ethnicity, Stookey in the comics is an Elderly Caucasian while the series has him as a Young African-American. The idea of an illness occurring and killing survivors has also been invented for the show as the comics hasn't explored that concept. Rick & Tyreese do engage in a fist fight but it is Tyreese who ends 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 Chambler's 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 & April Chalmers(Daughters), the TV series however only features David & Tara, April's name was change to Lilly who is a woodbury resident from the comics that plays a vital role and is the main character in the second novel series titled "Road to Woodbury" and there was no Meghan Chambler 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 Philip after he kills her zombified father in the novel while in the series she understood and was okay with Philip/The Governor after killing her zombified father. In addition, The Governor never gets romantically involved with April/Lilly but rather it was his brother who does(and accidentally rapes her during their encounter) which resulted in Tara throwing them out, the remaining Chalmer's sisters never returned in future storylines after throwing out The Governor and his group.
Caesar Martinez's death plays out differently than his comic counterpart's, he died before Woodbury's first attack on the prison in the comics as he was killed by Rick Grimes after Martinez helps him, Michonne and Glenn escape from Woodbury only to run off back to Woodbury after learning the location of the Prison in which Rick believes he betrayed his trust and went off to inform The Governor of their location as Martinez claimed he went back to bring the good people to the prison 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 Prison assault 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 Prison assault, Tyreese was decapitated in the second prison attack, unlike the TV series, comic Michonne was never present when the decapitation took place as she was never captured and she was never present in the final prison attack. Hershel Greene is killed by The Governor in the comics but with shot to the head, in the TV series he takes comic Tyreese's place and was decapitated in the final prison battle with Michonne present as they were both captured during a supply run instead of assassination attempt in the comics. Maggie & Glenn were never present in the second & third battle as they 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 fist in the comics as The Governor was smaller & 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 came to the realization that he was bad and in turn killed 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 & 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 & Carl only to breakaway from them, in addition Rick only suffered two casualty's resulting in The Governor's attack. Also noting not all of The Governor's people(who had no military training) were killed in the comics, the remaining were led to the Prison by Lilly Caul after his demise, the third novel titled "The Fall of the Governor" tells you what happened to Lilly Caul and her group. In the TV show, all The Governor's people(who are military experts) were killed, only Lilly & Tara survived the battle. The Prison survivors split up into 5 groups, in the comics, it is only 2 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, 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.
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, and 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.