Los padres de Drake y Josh se van de crucero por diez días, dejándolos a cargo de todo. Pero Drake y Josh meten a su hermana pequeña Megan en el vuelo equivocado a Los Ángeles, cuando se suponía que debía visitar a su amiga Jessica en Denver, Colorado; y deciden entonces ir a buscarla.
American football coach Chuck Dichter has worked wonders with the Buffalo Bills, and is even confident to crown his career with a Super Bowl victory, but before the play-offs an oyster food-poisoning wipes out his first team for a month. Dan Heller, an insurance salesman and former college quarterback, who was hired -relactantly, but his wife twisted his arm- just for practice, now has to captain and train a bunch of rookies and old-timers against the hardest adversaries. Dichter decides to sign up triple Super Bowl-winner Tommy Baker in Dan's place...
