故事发生在17世纪，传说中海盗最为活跃的加勒比海。风趣迷人的杰克·斯伯洛（约翰尼·德普 Johnny Depp 饰），是活跃在加勒比海上的海盗，拥有属于自己的“黑珍珠”号海盗船。对他来说，最惬意的生活就是驾驶着“黑珍珠”号在加勒比海上游荡，自由自在的打劫过往船只。但不幸的是，他的仇敌，老谋深算的巴尔巴罗萨船长(杰弗里·拉什 Geoffrey Rush 饰)偷走了他的“黑珍珠”号。巴伯萨是一个无恶不作的坏蛋，他抢劫了杰克的"黑珍珠号"后，更加猖狂，在加勒比海上横行霸道，一时成为整个加勒比海的霸主。
　　一次，巴伯萨一伙袭击了罗亚尔港小镇，还绑架了总督的女儿伊莉莎白·斯万(凯拉·奈特莉 Keira Knightley 饰)和伊莉莎白青梅竹马的铁匠学徒威尔·特纳（奥兰多·布鲁姆 Orlando Bloom 饰），想方设法救出了狱中的船长杰克，偷来英国皇家舰队最快的"拦截号"军舰迅速向"黑珍珠"追去。
　　在打斗中，威尔和杰克发现，巴尔巴罗萨和他的海盗们身背着咒语，在每一个月光之夜，他们就变成了不死骷髅，而伊莉莎白正是解开咒语的关键。

Sometime in the near future, paraplegic prison inmate Matt Mills meets "The Board" of Satoshi-Telefair Industries, who thank him for joining the Program. Under pressure and with a promise to make him walk again, Mills agrees to volunteer. He is injected with a synthetic nanomaterial and suffocated, only to wake up with restored use of his legs, yet alone in a steel cell in the first spoke of an experimental apparatus - The Wheel. A series of assailants inflict a multitude of damage to Mills' body and torment his mind, yet the synthetic nanomaterial not only restores his damaged organs, it re-engineers his strength. The experiment might be designed to kill, but Mills is determined to survive - and get back to his daughter before The Board finds her first.

Whenterroristsplantabombonacommercialflight,thepassengersaboardtheplanemustfighttokeeptheplaneintheairandallthepassengersalive:thebombisriggedtodetonatewhenevertheplanedipsbelow800feet.