The movie begins with Paige Collins (Rachel McAdams) and her husband Leo (Channing Tatum) coming out of a movie theater. On their way home, when they stop at a stop sign, Paige unbuckles her seatbelt to lean over and kiss Leo. At that very moment, a truck rams their Saab 900 from behind and Paige crashes out through the windshield. Both of them are rushed to the emergency room, and as Leo, in a voice-over talks about how "moments of impact.. help in finding who we are" the movie cuts to how Paige and Leo first met. The scenes of how they courted, proposed and married are interwound with the present.
When Paige regains her consciousness, she thinks Leo is her doctor, implying her loss of memory.
Paige verifies what her remaining memories are when she starts a conversation with Leo. She learns she has not lost all, except for the past few years of her life given she still remembers that she wanted to be an artist in high school. Paige is unable to figure out why she left law school.
Later her parents learn about the accident and come to visit her and it is for the first time that Leo meets them. They learn that the doctor recommends she return to her normal routine but her parents and Leo disagree about what her normal routine is at the present time. Leo tells Paige that she stopped talking to her parents before the accident mostly because her father insisted she attend law school while she attend art school. Paige is unable to understand why she broke off the engagement with Jeremy. Leo tries to persuade her to return home with him but she asks for proof such as a diary. He confirms that he does not know of such a diary existing before the accident.
Her parents insist on taking her home with them and Paige agrees assuming she might have married Leo for some mutual benefit. Just as she's about to leave, Leo comes running to play her a voice message in which she sounds very happy and romantic. Paige decides to go back with Leo hoping it will help her regain her lost memory.
On the drive to their home, Paige learns from Leo that the American president is Obama. She recognizes him as the senator. Leo states that she voted for him.
Paige is welcomed home with a surprise party by her friends but as she's not able to remember any of them, she finds it overwhelming and isolates herself from the party. She expresses her anger at the situation to Leo after the party is over and everyone leaves their home. Paige asks him to leave her alone so he complies with her request.
The next day Paige appears dressed in a Chicago Cubs hoodie and she says it's the only piece of clothing she owns that she feels comfortable putting on that morning. Leo informs her that it is actually owned by him. She grabs a piece of bacon and she puts it in her mouth but he informs her that she is vegetarian.
Paige reassures Leo that she is fine and she tells him to go to his job. He reluctantly accepts her advice and he leaves her alone at home. Paige continues to eat the bacon once he has left for work.
Paige discovers more evidence of her marriage with Leo while she is alone at home. These come in the form of a video recording of her wedding. She spots the Cafe Mnemonic menu in her hand while she is watching the video.
Paige ventures out to Cafe Mnemonic but does not remember being there and loses her way back. She calls up her mom as she does not know or remember Leo's number.
That evening Leo and Paige are invited for dinner by her parents. Paige's mom brings out filet mignon and she announces it is Paige's favourite dish. Paige accepts it happily despite Leo's puzzled expression.
At the dinner and in the bar later, Leo does not fit in with her family and friends. Leo keeps trying to help her regain her memory but Paige is more drawn towards finding answers as to why she left law school or broke the engagement. And, in one such occasion with Jeremy, she kisses him.
Leo attempts to get closer to Paige by tickling her like he did before the accident. The plan fails as she does not remember the ritual.
Leo takes Paige to her art studio the next morning. He turns up the music in an attempt to jog her memory when he asks her to complete a piece of artwork. This plan also fails when the music only succeeds in giving her a headache.
Her doctor advises her to fill the holes in her memory rather than be afraid of her past. With her sister Gwen's wedding approaching, Paige decides to stay with her parents until the wedding. Leo asks her out on a date and she accepts his proposal. He successfully spends the night with her and it ends with them making out before he takes her home.
Leo returns home to find a stack of overdue bills waiting for him. After Gwen's wedding, Paige's dad confronts Leo about his debts and he concludes that Leo's best solution is to divorce his daughter. Leo punches Jeremy for talking about sleeping with Paige. Afterwards Leo confronts Paige and they agree that their relationship has reached its end.
Paige rejoins law school and Leo signs the divorce papers. At a store, she meets with a former friend of hers whom she recognizes as Diane immediately. Diane apologizes for having a relationship with her dad; and Paige now realizes why she had left her family. When Paige confronts her mom about deceiving her, her mom tells her that she decided to stay with her dad for all the things he had done right instead of leaving him for one wrong act. Paige concludes that she must stay away from her parents in order to recover her true identity.
Paige then asks Leo why he never told her and he replies he wanted to earn her love instead of driving her away from her parents. Paige, while in class, starts sketching; thus depicting how she first left law school. She does it again and is back into sculpting and drawing. Though Jeremy confesses he broke up with his present girlfriend, hoping to be back with her, she turns him down stating she needs to know what life would be without him. Jeremy confesses to Paige that she dumped him the first time for a similar reason.
And as seasons change, Leo, in a voiceover talks about "moments of impact and ripple effects bringing unpredictable change where some particles are brought crashing together, closer together while others are sent farther away." Back in her room, Paige finds the menu card on which she had written her vow and is deeply moved. The movie ends with Paige waiting for Leo at a closed Cafe Mnemonic and going with him to try a new place instead of their regular alternative, a Cuban place.