It's Valentine's Day in Los Angeles, florist Reed Bennett (Ashton Kutcher) proposes to his girlfriend Morley (Jessica Alba) who accepts, much to the surprise of Reeds closest friends Alphonso (George Lopez) and Julia Fitzpatrick (Jennifer Garner). Morley changes her mind and leaves Reed later in the day. Alphonso tells Reed he and Julia knew it would never work out between him and Morley, and Reed wishes they had told him. On an airplane to Los Angeles, Kate Hazeltine (Julia Roberts), a captain in the U.S. Army on a one-day leave, befriends newly single Holden Bristow (Bradley Cooper). Kate and Holden chat, play a backgammon, and tell jokes. When the plane lands, and Kate has to wait hours for the taxi, Holden offers his limousine, which Kate accepts, as she only has one day to spend with her family before she has to go back to the army.
Julia, an elementary school teacher has fallen in love with Dr. Harrison Copeland (Patrick Dempsey), but does not know that he is married to his wife Pamela (Katherine LaNasa). Reed finds out when Harrison orders flowers for his wife and girlfriend, Julia (Jennifer Garner). Harrison tells her that he needs to go to San Francisco for a business trip. Wanting to surprise him and following Reed's advice from earlier on in the day, Julia buys a plane ticket to San Francisco. Reed quickly comes to the airport and warns Julia, and she refuses to believe it and gets on the plane. She goes to the hospital where he said he would be, and inquires after him. The nurses at the counter reveal to her that he is married and tell her the name of the restaurant where he and his wife will be dining that evening. As she teaches the owner's son, the owner allows her to dress as a waitress. Julia makes a scene at the restaurant, and gives back the toy Harrison gave her that morning. Harrison's wife, Pamela, becomes suspicious when Julia makes a comment referring to Harrison's ability to juggle, and Harrison is seen eating pizza alone in a condo later on that evening, implying that Pamela has left him right after Julia's scene. One of Julia's students, Edison (Bryce Robinson), orders flowers from Reed, to be sent to his teacher. There is a delay in the delivery of flowers, but Edison insists that Reed delivers the flowers the same day. They are for Julia; however, she suggests to Edison to give the flowers to a lonely girl in the class who also has a crush on him, which he does.
Edison's babysitter Grace (Emma Roberts) is planning to lose her virginity with her boyfriend Alex (Carter Jenkins). The planned encounter goes awry when Grace's mom discovers a naked Alex in Grace's room rehearsing a song he wrote for Grace on his guitar. Meanwhile Edison's grandparents, Edgar (Hector Elizondo) and Estelle (Shirley MacLaine) are facing the troubles of a long marriage. Grace explains to them that she wants to have sex with Alex, and says, "It's not like I am going to sleep with one person for the rest of my life." This upsets Estelle and leads to her telling Edgar about an affair she had with one of his business partners. The affair was while he was away, and it didn't last long. Although she is deeply sorry for what she did, Edgar is deeply upset. Graces high-school friends, Willy (Taylor Lautner) and Felicia (Taylor Swift), are experiencing the freshness of new love, and have agreed to wait to have sex. On Valentine's Day, Willy gives Felicia a large white bear that she carries around with her everywhere and Felicia gets him a gray running t-shirt (which was his) and ironed the number 13 on the back for "good luck". They are interviewed on the news and advertise their love and support for each other.
Sean Jackson (Eric Dane), a closeted gay professional football player, is contemplating the end of his career together with his publicist Kara (Jessica Biel) and his agent Paula (Queen Latifah). Kara, a close friend of Julia's, is organizing her annual I Hate Valentines Day party, but is becoming interested in sports reporter Kelvin Moore (Jamie Foxx) who has been sent out by his producer Susan (Kathy Bates) to cover Valentines Day because of a lack of sports news, and they share their mutual hatred of Valentine's Day. Paula has hired a new receptionist named Liz (Anne Hathaway) who has started dating mailroom clerk Jason (Topher Grace). Jason is first shocked when Liz turns out to be moonlighting as a phone sex operator. Liz explains that she is only doing this because she has a $100,000 student loan to pay off, has no health insurance, and is completely broke. Jason decides that her job is too much for him to handle, but eventually comes back to the relationship after seeing Edgar forgive his wife, Estelle.
Sean comes out on national television, and Holden (who is Sean's lover) goes back to him. Kate goes home to greet her son Edison. Willy drops Felicia off at home after a date and they kiss goodnight. Kelvin and Kara hang out at Kelvin's news station where they later kiss, Alfonso dines with his wife, Grace and Alex agree to wait to have sex, Edgar and Estelle retell each other their marriage vows and kiss in the theater, Jason goes back to Liz and they decide to keep a bond together but to also "keep it simple", Morley is shown walking her Border collie while trying to call Reed and the movie closes with Julia and Reed beginning a relationship.