Gary Grobowski (VINCE VAUGHN) is a charismatic tour guide for a Chicago tour bus business he runs with his brothers Lupus (COLE HAUSER) and Dennis (VINCENT D'ONOFRIO). Brooke Meyers (JENNIFER ANISTON) works alongside receptionist Christopher (JUSTIN LONG) at an art gallery named after the proprietor Marilyn Dean (JUDY DAVIS).
The two meet at a baseball game, he sweeps her off her feet, they fall in love and buy a highly desired condo together. But things then quickly turn sour when Brooke realizes Gary doesn't appreciate her and the things she does for him, while he thinks all she does is nag him and refuses to let him get a pool table for their place.
Accordingly, she turns to her married friend Addie (JOEY LAUREN ADAMS) for advice, all while getting moral support from her flamboyant brother Richard (JOHN MICHAEL HIGGINS) who belongs to an all-male a cappella group, The Tone Rangers. Meanwhile, Gary confides in his best friend Johnny O (JON FAVREAU), while their real estate agent friend Riggleman (JASON BATEMAN) finds himself stuck in the middle since he sees a lucrative commission should they decide to sell.
But neither wants to give up the place, and thus a war of wills soon escalates between the two. From that point on, and as their relationship further disintegrates, Gary and Brooke find themselves torn between their love that once was and their desire to drive the other out of their place.