As the studio credits roll, a pop tune starts playing and it turns into the ring tone for Carl Allen (Jim Carrey). Carl sees 'Unknown Caller', which he ignores until he accidently answers the call. Carl is talking to his best friend Peter (Bradley Cooper) who is trying to persuade him to come to a gathering at the usual bar and Carl keeps trying to weasel out telling Peter that he's at home and he's got things to do but is really at the local Blockbuster renting movies like 300 and Transformers for a lonely night at home. During the conversation, we see Peter outside the store window, and Carl is caught.
Carl ends up going to the bar with Peter, Rooney (Danny Masterson from That 70's Show) and Lucy (Sasha Alexander). Peter makes the big announcement that he and Lucy are engaged and tells Carl the date of their engagement party, which Carl is obligated to attend. While this is going on, Carl looks over at the bar to see Stephanie (Molly Sims). Stephanie is Carl's ex-wife and it's been three years since their split. He tries to excuse himself but they come over and chat for a bit and he's introduced to her new boyfriend. He tries and makes a graceful exit but doesn't bumping into the waitress with a tray full of drinks and then slipping on the wet floor.
The next morning, we see Carl get dressed in a bland suit, pick up a name tag and head out the door to his job as a junior loan officer at a bank. As he closes his door, a nice elderly woman named Tillie asks him if he wants some breakfast and invites him over, and Carl declines. As he heads to work, he meets a homeless man and declines him help, gets his coffee and declines a flyer to come see a local band and ends up in front of his computer declining emails and websites for Middle Eastern wives.
At work, we meet his boss Norman (Rhys Darby). Norman takes a call at Carl's desk and it turns out that Carl was passed over for a promotion. A guy then comes in and asks for a loan to start a business of making "Roller Blade Suits". He is desperate and has no other options but Carl denies his claim. As he sits outside and ponders his existence, he meets an old co-worker Nick (John Michael Higgins) who left the rat race to "live". He's traveled exotic places and done incredible things and he attributes this to being a "Yes Man". He invites Carl to the next 'Yes' conference and makes him take a pamphlet.
We then see a montage of Carl living out his mundane life renting movies and watching them and in the middle of the movie 'Saw' (the part where he's cutting off his own leg, please see spoiler for Saw), Peter comes in and tells him he missed the engagement party and he's upset at Carl. As he leaves, he tells Carl to do something about his life or he'll be alone.
Immediately after this, Peter and Rooney enter Carl's apartment and make comments of how dead Carl looks. It turns out that this was only a nightmare and as Carl wakes up, he opens the 'Yes' Conference pamphlet and he decides to attend.
As he walks through the lobby of tables and booths holding a 'Yes' tote bag, he walks into the conference room and sits down. Amazingly, Nick is in the same row and comes over to sit with Carl. As the conference begins, there is a montage of images with the philosopher of the so-called 'Yes' Guru, Terrance Bundley (Enter, Terrance Stamp). He starts his 'Yes' chanting and what not and welcomes everyone, especially those that are there for the first time and as he continues to ask who is there, Nick shouts out that Carl is there for the first time. Terrance asks Carl to come to the front and when Carl declines several times, Terrance takes off his shoes and runs to him from the stage. As he confronts Carl, every time Carl says no, the crowd starts chanting, "No-man! No-man!" and every time he says "yes", the crowd screams, "yes!" After bantering with Carl for a while, Terrance makes a 'covenant' with Carl to say YES at every opportunity and Carl hesitantly agrees.
As Carl and Nick are walking away from the conference, people congratulate Carl on his breakthrough. Just then, a homeless man (Brent Briscoe) mentions how nice his BMW is and asks Carl for a lift to the park. Encouraged by Nick, he agrees. In the car before they leave, the homeless man asks to use Carl's phone and Carl agrees. On the ride to the park, the homeless man is laughing with someone on the phone, while Carl is asking where in the park to drop him off. The cell phone battery dies and the man thanks Carl. Before the homeless man shuts the door, he asks Carl for a few bucks. The new Carl reluctantly says 'yes' while taking out a wad of bills... he ends up giving the guy the money and the guy thanks him and runs into the bushes with a head first dive. As Carl tries to drive away, his car runs out of gas.
We see Carl talking to himself all the way to the gas station. While filling up his gas can, a woman on a scooter pulls in and takes a Polaroid of him bent over filling his gas can. They make small talk and she offers him a ride, to which he says yes. While riding the scooter, she takes another picture, this time of both of them and drives him to his car. Carl seems to be enjoying this somewhat. As they are about to part, he says under his breath if they want to make out and she hears this, walks over and kisses him... after riding away, Carl looks in his hands and sees the Polaroid of the two of them.
The next morning (Saturday), he reflects on his adventurous night and he smiles. Just then the phone rings and without hesitation, he picks it up and it's Norman asking if he can come to work, and the new Carl of course says "Yes!" As he leaves his apartment, Tillie bumps into him and asks if he could help her put up some shelves, to which he agrees. After finishing she wants to give him money but she didn't go to the bank so she offers to help him 'release' but he declines and leaves. As he closes the door, it closes on his shirt and he wonders if it's because he broke the covenant with Terrance. When he yanks his shirt free, he falls down the stairs to a waiting dog who is barking viciously at him. So he picks himself up and reluctantly agrees to Tillie's 'payment'. As he's lying on his back in her frilly bed, she begins to go down on him. Carl looks over at her nightstand and sees Tillie put her dentures into a cup of solution. Throughout the blow job, Carl has a wide variation of facial expressions, and although he is disgusted by her age and the fact that she has no teeth, he is loving the feeling.
When he finally gets to work, he begins to click 'Yes' to spam emails advertising penis enlargement and ordering a Middle Eastern wife. While he's doing this, a woman approaches his desk with a large box and asks for a loan to start a cake making business. She explains that she makes cakes that resemble the heads of famous people. Carl then mistakes the cake sitting on his desk for Bono, when it is actually Mickey Roderek. With his new found philosophy, he says 'yes' to her loan and then as he's explaining it to Norman, Norman hints at a promotion that he didn't get earlier because he said 'yes to too many projects. Further to this, accepts Normans invitation to dress like a character from Harry Potter.
He goes back to the Bar with Peter and Rooney, where Carl apologizes to them, especially Peter, for missing out and being a recluse. Then, Carl begins sharing the 'yes' philosophy, and the guys toast to Carl's effort. Peter offers Carl to start a tab paying for their drinks, and Carl agrees. In the next scene, their table is full of empty glasses and Carl accepts the dare to snort hot sauce. Carl is wasted and as they begin to leave, a woman asks if she can... and before she finishes the sentence, Carl grabs her and passionately kisses her and then spits out the gum she was chewing. Her boyfriend then comes over and Carl goes into a monologue about how beautiful girls deserve to go to a Ball and the two end up fighting in the alley. Carl gets completely beat up and wakes up the next day on the floor of the bathroom with his legs wrapped around the toilet.
The next day we see a montage of Carl saying yes to a guy who wants to start a fertilizer business and taking the flyer from the guy to see the band, to taking guitar lessons, to taking Korean language lessons, and Flying lessons (okay, all of these are important later). After seeing him do take guitar lessons, flying lessons, and taking Korean classes, he shows up at the club to see the band and they are a weird psychedelic, kind of campy throw back band (two members wearing seahorse hats) and there are about 6 regulars who come to watch them perform and the lead singer is... Scooter girl from the park! (Her name is Allison, played by Zooey Deschanel) After the show, he offers her a drink but she says no because she has a yoga/jogging/photography group she leads (she seems like a free spirit) and so Carl walks her to her scooter and accepts an invite to the group, which meets at 6am. That night as he sets his alarm and turns off the light, Rooney calls and asks if he wants to join them on an all-nighter with multiple cases of Red Bull, which of course Carl says Yes.
The next morning at the jogging group, a car screeches in and out jumps Carl pepped up on Red Bull and saying goodbye to Lee, who is an Asian male Registered Nurse. He attends the group and he goes on a love rant about Red Bull and Allison mentions that there's a hard crash with those things but Carl doesn't care and takes off jogging and taking pictures at the same time... the group is having a hard time keeping up until they see Carl crashed on the ground holding his camera... the group then start taking pictures of him. After the group is done, we see Carl and Allison talking and it's revealed that a guy dumped Allison when things got too serious and there's an obvious spark.
We then cut to a funny scene where Carl is having lunch with Peter and his new Middle Eastern bride Faranoosh (Anna Khaja) and they whisper about Allison even though Faranoosh can hear... Lucy then shows up and is disappointed that no one can help her with her bridal shower so Peter asks Carl and of course he agrees even with a 'look' from Faranoosh.
At the bridal store, a surly Korean woman Soo Mi is helping them and Carl then engages her in a conversation as to why she is unhappy (in Korean) and she tells him that she sees all these couples but she can't find anyone... just then a man comes in shouting in Korean that a man is standing on the ledge ready to commit suicide... Carl springs into action and the Suicide man (great cameo by Luis Guzman) seems to be on his last string and instead of talking him down, Carl hesitates and asks Suicide man to hold on and we see him go and tune a guitar and he comes back and sings "Jumper" by Third Eye Blind... and sings him down from the ledge... The whole crowd was watching and joining in the singing...
We see a door and a knock and Norman opens it dressed like Ronald Weasley and Carl is there with Allison (Harry Potter and Hermione Granger) and they see everyone from a guy wearing a Hagrid costume to a guy with a full blown Dobby the Elf costume and mask (for all the character, please see spoiler for the Harry Potter movies) and seems like a great party with them watching all the Harry Potter movies (and Norman reciting line for line with the movie). Afterwards, Allison lets Carl drive her scooter and he ends up taking her to the Hollywood Bowl (concert hall) and they sneak in and he starts to sing a Beatles tune and they make out and then sit in the stands and talk about Allison's band and stuff... they really connect here and are caught by an old guard... as the guard tells them to Stop, Carl does and when Allison says lets go, he does and this goes back and forth 'til he says, he can't please everyone!
The next morning at work, Carl now has a line of people waiting to seek a loan and Norman tells him an executive is here from the Head Office and that they may be in trouble for saying yes to all those loans... Before going up, he sees Lee (the Registered Nurse) in his office and having an idea that he may be fired, Carl approves Lee's loan for a Ducati Motorcycle and heads upstairs (Important Later). The bank executive seems like a hard ass about these small loans but mentions that people are so grateful, 98% of them are making good on their payments and the bank is making lots of money... and so Carl gets the promotion to the Board room and Norman does not, although Norman was the manager who approved Carl to do these...
We now see Carl at the airport and he runs into Stephanie and her boyfriend on their way to Tahiti, where his family owns 100 acres (seems like a pompous rich guy, who corrects Stephanie about it being a small piece of land). Stephanie mentions how he saw Carl on the news about saving the Suicide mans life and asks where he is going and he replies he and Allison are just traveling wherever and as they leave, she glances back at him...
At the airline counter, they just ask for tickets on the next boarding flight and it's to... Lincoln, Nebraska. So they go and visit a museum of telephones, watching a University of Nebraska College Football game (face and body paint! and Peter, Rooney and Lucy see him at the game...) and end up walking on a gravel road and when it starts raining, they take shelter in a barn and she reveals she's in love with him and suggest they move in together and before saying yes, he pauses, which she notices but they hug with him in deep thought.
At the airport, they try to fly again but then are detained by the FBI who have been tracking them since he made the initial flight to Nebraska and they ask they begin to interrogate him asking him why he gave a loan to a fertilizer business man, why he's taking Korean lessons (North Korea connection), why he's taking flying lessons and why he was only married for 6 months... all in ear shot of Allison... he calls for his lawyer, Peter who explains that he's following a new philosophy of saying Yes to everything and Allison hears this and thinks that's why he paused because he had to and not wanted to see her and be with her... she leaves him behind and breaks up with Carl.
Back home, Carl gets a call from Stephanie who says her boyfriend left and asks him to come over, to which he does and while explaining what happens, she starts to kiss him and she asks him to stay... but he says No! As he is leaving, bad stuff starts happening and he wonders if it's because he broke the covenant... He tries to get Allison back but she tells him to go jump off a bridge and he does by bungee jumping. As he is hanging upside down, he gets a call from the Bank executive telling him to close down some branches including his old one, so he visits Norman who is having a '300' themed party and give him the bad news and Norman breaks down crying... Carl then gets home to his answering machine only to be reminded that he has to throw Lucy a bridal shower and it's the 11th hour... it looks like he's about to 'fess up to them when they walk into the bar and are greeted by a multitude of people... turns out that Carl called up all his loan favors and asked them to come to the bridal shower... at the shower, he hooks up Norman with Soo Mi, Rooney ends up agreeing to do a favor for Tillie (knowing how good she is...) and Carl and Peter talk about things and how Allison doesn't want him back and realizes that maybe he broke the covenant... so he hurries out and sneaks into the back of Terrance the Guru's car (who is just coming out of a conference) and as Terrance beings to drive away, he is startled by Carl and steps on the gas into traffic and the car is hit...
In the hospital, Carl is confronted by Terrance and Terrance says that since he was being so negative, he had to do something so that he doesn't look bad... but the Yes part was all a principle and that Carl needs to show discernment in what he says yes to! With that note, Carl storms away wanting to see Allison and Rooney tells him it's 5:40am just before her morning class... He bumps into Lee who give him the keys to the Ducati and he takes off for the group... once at the group, he screeches smoke into the air and there's a cool slow motion coming out of the smoke scene and Carl tries to explain everything to Allison including that he doesn't want to move in right now but that he loves her and wants to be with her... this while the group is taking their pictures inappropriately... the movie ends with them kissing.
During the end credits: A guy in an SUV is thanking Carl for approving his loan and it's the guy from the beginning who was rejected... Carl and Allison are now suited up with Roller Blades and they go blading down the road on their stomachs a la Olympic Skeleton-ing... and fades to black.