Eddie (Ben Stiller), the owner of a sports shop, is single but ambivalent about starting a relationship. While walking down the street he sees a thief snatching Lila’s purse. Eddie tries but fails to retrieve the purse, he and Lila (Malin_Åkerman) exchange pleasantries, eventually begin dating, and soon become serious. Each of the two imagines it’s a perfect match. When a job offer to Lila threatens to move her to Holland, Eddie learns that the company would not move a married employee, and with the urging of both his father (Jerry Stiller) and his best friend (Rob Corddry), Eddie marries Lila.
During their honeymoon, it becomes increasingly apparent to Eddie how mismatched they are. On the drive to Cabo San Lucas, Lila irritates Eddie with incessant singing to a blasting radio. Lila’s sex is so strenuous that Eddie suffers physical pain. Eddie’s disaffection deepens when Lila divulges her history of cocaine abuse, a deviated septum, and her habit of spitting her drinks out through her nose. He learns that her professional position is that of only a volunteer, and that the purse snatcher had been one of her former lovers.
At the Los Cabos resort, Lila adamantly refuses to use sunblock while sunbathing only in baby oil, and then blames Eddie for the agony of her first-degree sunburn. As the enormity of Eddie’s mistake sinks in, he meets Miranda (Michelle Monaghan), a vacationer with her family from Mississippi. Just as with Lila, Eddie immediately imagines that he and Miranda are a perfect match. With Lila confined to her room crippled by sunburn, Eddie devotes most of his honeymoon to Miranda. Eddie makes a favorable impression on all of her family except for her cousin, Martin (Danny McBride), who senses that Eddie is hiding something. To explain his often absence to Lila, Eddie fabricates a story about a major supplier to his business, for which he’s working out “better credit terms.”