On a distant planet that's inhabited only by a technologically advanced, all-male race that reproduces by cloning, a candidate is being chosen for their latest effort at total domination of the universe. Their leader, Graydon (BEN KINGSLEY), wishes to take over Earth from the inside, and thus plans to send one of his finest men to breed with an Earth woman, thus setting into motion their conquest.
As such, and after much training, H1449 (GARRY SHANDLING) is chosen and travels to Earth in the guise of Harold Anderson, an Arizona-based commercial and home loan officer, whose sole mission is to find and impregnate the first available woman.
While his banker coworker Perry Gordon (GREG KINNEAR) -- who regularly cheats on his wife, Helen (LINDA FIORENTINO), whenever he gets the chance - applauds Harold's straightforwardness regarding sex, none of the women the alien encounters fall for his obviously stilted pickup lines. While he eventually meets a few receptive women, including Rebecca (JUDY GREER), a flight attendant, and Cheryl (ANASTASIA SAKELARIS), a strip club waitress, they get nervous from the humming sound that emanates from the artificially attached penis given to him to complete his mission.
Things change when Harold happens to meet Susan Hart (ANNETTE BENING), a real estate agent and recovering alcoholic who's starting to put her life back together. Since she senses her biological clock ticking, she falls for Harold's lines about being put on Earth to have a child and the two soon become an item.
Yet, she won't have sex until she's married, thus creating quite a dilemma for Harold. From that point on, he must not only contend with that, but also his competition with Perry at work for a new job, the efforts of FAA agent Roland Jones (JOHN GOODMAN) to prove that Harold's an alien, and the general differences between men and women, all of which serve to complicate his efforts of successfully completing his mission.