Kirk Kettner (Jay Baruchel) is a native of Pittsburgh, Pennsylvania in his mid-20s who has low self-esteem and, by his own admission, has not accomplished very much in life. He works at the Pittsburgh International Airport as a Transportation Security Administration officer, and hopes of becoming a pilot one day. He tries to get back together with his self-centered ex-girlfriend, Marnie (Lindsay Sloane). Marnie ended her relationship with Kirk two years ago and is highly dismissive of his continued romantic interests after his latest pursuit. However, she has remained close with Kirk's parents (Debra Jo Rupp and Adam LeFevre) and overbearing brother Dylan (Kyle Bornheimer), continues to participate in family activities along with her new boyfriend Ron, and even lives with Kirk's parents. He has three close male friends who also work at the airport: Stainer (T. J. Miller), Devon (Nate Torrence), and Jack (Mike Vogel).
Then at work one morning, a beautiful woman, Molly McCleish (Alice Eve), arrives at the passenger terminal for a flight to New York. While proceeding through security, her striking looks attract unwanted attention and harassment from several male employees. Kirk is the only employee to treat her courteously. She and Kirk exchange a few innocuous words, and she then proceeds to her flight, accidentally leaving her phone in the airport security area. Upon realizing she has misplaced it, Molly calls her phone and Kirk, back at the security checkpoint, answers. The two arrange for a time to meet the following evening so that he may return the phone to her.
The following night, Kirk arrives at the Andy Warhol Museum where Molly, a professional event planner, is running a party. Devon accompanies Kirk to the Museum where Kirk returns Molly her phone. After returning the phone, both stayed and met Katie, Molly's sister. Katie then on purpose causes Kirk to spill his drink on the museum director and is asked to leave the museum for being uninvited for the party. Molly offers tickets to Kirk to the Pittsburgh Penguins hockey game at the Mellon Arena as an apology. Molly then subsequently gets herself invited to Kirk's family lunch. This incurs jealousy in Marnie, who feels upstaged by Molly's looks and takes a sudden interest in Kirk again. Stainer, ranking-obsessed, tells Kirk that on a scale from 1 to 10 with 10 meaning the most attractive and successful, he's a 5, and Molly a 10, and that a relationship does not work if the difference is more than 2. Molly's friend and business partner Patty (Krysten Ritter) is also surprised: she phoned Molly while on a date with Kirk to allow her an opportunity to make up an excuse to leave, but that was not needed.
In Molly's house, while the two are making out, Kirk ejaculates in his pants, just before her parents arrive. While avoiding to show that he had ejaculated, he avoids standing up and quickly leaves to avoid Molly and her parents noticing what happened. This cools down the relationship, but when Kirk later explains during an airshow what happened, things are fine again. Molly's former boyfriend Cam tells Kirk that Molly has a defect and to avoid saying that she is perfect.
During a date, Kirk suggests to Molly to throw a birthday birthday for her sister, Katie. After the party, both of them go to Molly's place. Molly shows Kirk her webbed toes, which Kirk considers so minor that he decides that she is too perfect for him, and he breaks off the relationship. Kirk and Marnie resume their relationship and go on a family trip to Branson.
Stainer and Patty realize their mistake in telling Kirk and Molly it wouldn't work out; the friends convince Kirk that he is "a 10" too. They pull Kirk off his plane as he tries to leave with his family and Marnie, while Patty brings Molly to the airport. Kirk rejects Marnie and reunites with Molly. Later, as a surprise, he takes Molly on a trip in a small plane, with himself being the pilot; he has taken flying lessons.