The film begins with Paige (Rachel McAdams) and Leo (Channing Tatum) coming out of a movie theater. It is snowing. They get in the car to drive home, and they are laughing and joking as Leo sings along to the radio. At a stop sign, Paige says she heard that sex in cars is conducive to pregnancy. She unbuckles her seatbelt to lean over and kiss Leo.
At that moment, a huge dump truck rear-ends their vehicle, sending Paige crashing through the windshield in slow motion. As they are rushed to the hospital, Leo’s voice says “My theory is that there are moments of impact and high intensity that end up defining who we are.”
Flashback to the day that Leo and Paige first met. They are both waiting in a long line for a parking pass, and Leo follows Paige out to her car. He points out that they live in the same parking zone, and says that means they should go out on a date. They head to Café Mnemonic where they laugh and talk and feed each other truffles.
A montage of their relationship follows. Paige is working as a waitress, and she’s sick with a cold, so Leo leaves her a box of treats to make her feel better. Then they are driving in the car, laughing and joking with each other.
Back at the hospital, the doctor explains to Leo that they are keeping Paige in a coma to allow her brain to heal. Leo’s voiceover says “Each of us is the sum total of every moment we’ve experienced and every person we’ve know.”
Flashback to Leo asking Paige to move in with him, spelled out in blueberries on her pancakes. Then flash to their wedding day. Both wrote their vows on Café Mnemonic menus. They were married in an art museum, and had to run away from the security guards as soon as they were finished. Flash to Paige working on her sculptures in her art studio. Paige is extremely stressed about the huge commission she won, and Leo helps her de-stress by tickling her. They make love on the floor.
Back at the hospital, Paige is finally brought out of her coma. Leo is waiting to speak with her, and she seems okay, until she asks “Was anyone else hurt, doctor?” to Leo. She doesn’t recognize him. Leo explains that he is her husband, and she stares at the ring on her hand in shock. Leo’s voiceover says, “Moments define who we are. What if one day you could no longer remember any of them?”
Later, Leo is sleeping in the waiting room of the hospital. Paige comes and wakes him, and asks if he wants to get something to eat in the cafeteria. As they eat, she asks him about her life. He explains that they live in the city, and she is a sculptor. She only remembers being in law school.
Cut to Leo discussing the situation with his friends. They joke and say that it’s actually a good thing Paige lost her memory, because now she won’t remember any of the stupid things Leo has done.
Back at the hospital, Leo is surprised to see that Paige’s room is empty. She’s been moved upstairs to the VIP donor wing. He goes up to her new room and finds Paige’s parents fussing over her. It’s obvious that they have never met Leo. They want Paige to come home with them, but of course, Leo wants her to stay with him.
At the cafeteria again, Paige asks Leo what is going on. Leo says that she hasn’t spoken to her family in five years. Before Paige and Leo met, Paige had a big falling out with her parents. Her father was angry that she broke off her engagement with Jeremy and dropped out of law school.
Paige’s parents try to take her home, and Leo begs her to stay. Paige says, “But I don’t know you. I don’t even know that we were really in love.” Leo plays her a voicemail that she left for him, but she’s not totally convinced. Leo says, “You owe it to yourself to honor the decisions you made in the last five years.” Paige decides to give her life with him a try.
When Leo takes her back to their apartment, all their friends jump out and yell surprise! Everyone is super happy to see Paige, but she is totally overwhelmed and runs to the bedroom. Leo sends everyone home, but Paige is furious that he would be so insensitive to how overwhelming it was for her simply to come home to a strange apartment with a strange man. She tells him to get out of the room.
The next morning, Paige wakes up and is shocked to see she has a tattoo on her back. Leo also wakes and absentmindedly comes into the bedroom naked. Paige shrieks, but laughs. When she comes out to the kitchen, Leo has made her a nice breakfast to apologize. Paige takes a bite of bacon, and Leo says, “Oh, that’s actually for me, you don’t eat meat.”
Paige asks what Leo does, and he explains that he runs a recording studio. She asks what she does, and Leo offers to show her the art studio, but she’s not ready yet. She tells Leo just to go about his day as usual, and as soon as he leaves she eats the bacon.
Leo heads over to the recording studio, where his partner Lily tells him things are going to crap without him.
Back at home, Paige is looking at all the records and books on the shelf. She finds a DVD with a note that says “More evidence”. It is the wedding DVD. She watches as her former self reads her vows to Leo. Leo reads his in return: “I vow to love you in all your forms, to always remember that this is a once in a lifetime love. No matter what challenges may come our way, I’ll always find my way back to you.”
Paige goes out to explore their neighborhood, and heads to Café Mnemonic where the barista asks if she wants the usual. Meanwhile, Leo arrives home with flowers and sees that Paige has forgotten her phone. He heads out to look for her, and indeed, when Paige exits Café Mnemonic she is totally lost. She uses a store phone to call her mom.
When Paige comes home hours later, Leo is waiting frantic. Paige is dressed in chic preppy clothes that her mom bought while they were out. Paige says that her parents have invited them for dinner.
Paige and Leo drive to her parents’ house in fancy suburban Lake Forrest. Paige is excited to see all the streets and houses she remembers. They sit down to dinner with her sister Gwen, who has just gotten engaged. Paige’s mother has made Paige’s “favorite dinner” – filet mignon. Paige’s dad asks about Leo’s family, who are all dead. They ask about Leo’s job, and he explains his passion for music, but they all just stare at him.
After dinner, they head out to meet some of Paige’s old friends. Paige notices her old friend Diana sitting at a nearby table, but Gwen steers Paige away. Paige is thrilled to see her old friends, and even more happy to see her ex-fiancée Jeremy (Scott Speedman). She obviously still has feelings for him, and she totally ignores Leo.