"Mad cow became mad person became mad zombie" is how quick-footed, virginal twenty-something Columbus (Jesse Eisenberg) describes the worldwide epidemic that started with diseased hamburger and has now turned all but a random few into the cannibalistic undead. Thus begins "Zombieland," a gleefully whacked-out horror-comedy that is funnier and scarier than 2004's cult classic "Shaun of the Dead." While we are keeping count, it also plays both genres, separately and jointly, more successfully than the recent "Jennifer's Body," which unevenly meshed laughs with frights. Making their devilishly good feature debuts, director Ruben Fleischer and screenwriters Rhett Reese and Paul Wernick show full control of their tricky tone—sarcastic but serious when need be—and a loose plot that makes up for a lack of motivation and resolution through its sheer narrative originality.

Columbus has managed to survive the takeover—so far—by following a series of practical rules, including being good at cardio, avoiding public bathrooms, wearing his seatbelt, checking the backseat, and always double-tapping his latest zombie kill with an extra shot to the head. As he makes his way across a desolate landscape of abandoned cars and silent roads headed for his hometown in Ohio to see if his parents are still living, he joins forces with the straight-talking Tallahassee (Woody Harrelson) and, later, two con-playing sisters, Wichita (Emma Stone) and Little Rock (Abigail Breslin). When word comes that Ohio is a wasteland, Columbus opts to stay with his new pack as Wichita and Little Rock set their sights on the California coast. Just outside of Los Angeles sits Pacific Playland, an amusement park that, from what they hear, is zombie-free. They really ought to know better.

"Zombieland" opens like a comic-tinged version of 2004's "Dawn of the Dead" and then consistently surprises as it moves forward, reinventing itself again and again as the characters travel on and the ever-changing setting flutters by. The opening credits sequence—slow-motion shots of the world falling apart scored to Metallica's "For Whom the Bell Tolls"—is mesmerizing. A single shot involving an evil clown peering under a bathroom stall is so startling and creepy it might induce gasps in the coulrophobic. A flashback to the initial outbreak goes from romantic to foreboding to ghastly as Columbus wakes in his apartment to find his beautiful neighbor (Amber Heard) frothing at the mouth and hungry for his flesh. Wichita and Little Rock, cautious at first of getting close to anyone else, make multiple attempts at stealing Columbus' and Tallahassee's truck—they succeed the first time—before deciding the guys are not so bad and agreeing to carpool with them. A montage of the foursome's disparate car conversations as they each take turns driving is a hoot.

Once they arrive in Los Angeles, driving down a Hollywood Boulevard populated only by costumed zombified workers in front of Grauman's Chinese Theater, their travels take them to the thought-deserted mansion of Tallahassee's idol, Bill Murray. The extended set-piece that follows is one of the most deliriously ingenious and fall-down-funny of the whole year, featuring one priceless idea, interchange and one-liner after the next. For a roughly ten-minute segment, "Zombieland" surpasses merely auspicious and moves into the terrain of the downright brilliant. The action-oriented, guns-blasting climax taking place at Pacific Playland is also loads of fun, like the ending of 1983's "National Lampoon's Vacation" if the Griswalds had to contend with blasting away swarms of zombies while partaking in the thrill rides. Nothing is exactly solved by the end—the earth, after all, is decidedly apocalyptic—but the film does make the valid point that real family is what you make of it, not reliant on blood relations.

Jesse Eisenberg (2009's "Adventureland"), along with Michael Cera, has the market cornered for characters who are supposed to be unassuming, non-threatening underdogs, and he is the logic-bound glue that holds all else together as Columbus. His developing friendship with Tallahassee, sibling-like relationship with Little Rock, and romantic feelings for Wichita are all well-established. As the Twinkie-seeking Tallahassee, Woody Harrelson (2009's "Management") is all-business at first and then lightens up and grows lovable himself once he gets to better know his road buddies. When revealed, a tragedy from his life that he is still trying to deal with brings welcome dramatic layers to his macho exterior. As Wichita, Emma Stone (2009's "Ghosts of Girlfriend's Past") is an edgy but inwardly sweet foil for Eisenberg's Columbus, and Abigail Breslin (2009's "My Sister's Keeper") lets her hair down and embraces her gun-toting, tough-girl side as 12-year-old Little Rock. Playing himself (to what extent will be left for viewers to discover), Bill Murray (2008's "City of Ember") deserves applauding for having a self-deprecating sense of humor and making the most of the year's best screen cameo.

Playing like a useful survival guide to an undead outbreak, a guts-filled horror film that turns George Romero on his head, and a knowing, occasionally referential screwball comedy, "Zombieland" is a zippy blast. Enthusiastic and acerbic, the writing and handful of characters keep on keepin' on while depth remains light and mostly on the surface. The joy and creativity brought to the project is what is most appreciable, director Ruben Fleischer and cinematographer Michael Bonvillain (2008's "Cloverfield") injecting candy colors, innovation and veritable threat into what could have just been another predictable study in dystopian destruction. Escaping a zombie uprising might be hazardous business, but "Zombieland" also makes it ridiculously entertaining.