The Pennsylvania native moved to Southern California to attend USC. To finance his education, he began to work as a model and actor, appearing in commercials and as an extra in big-budgeted movie musicals like "Camelot" (1967) and "Hello, Dolly!" (1969). After receiving a master's degree in film, he made short films ("Peege" 1973, "Foot Fetish" 1974) before segueing to series TV. Kleiser began directing TV-movies with "All Together Now" (ABC, 1975), a docudrama about orphans, and went on to helm "Dawn: Portrait of a Teenage Runaway" (NBC, 1976), with Eve Plumb (of "The Brady Bunch") as a young girl sucked into teen prostitution. Kleiser also directed John Travolta in his first TV-movie, the touching "The Boy in the Plastic Bubble" (ABC, 1976) and garnered an Emmy nomination for the award-winning holiday-themed "The Gathering" (ABC, 1977), which featured Edward Asner as a dying man trying to make amends with his estranged family.

"Grease" (1978), a film adaptation of a long-running Broadway musical, was a fantasy version of the 1950s teen musicals. Kleiser seamlessly interwove the film's musical numbers with the plot machinations and elicited a strong performance from leading man John Travolta. The exuberant, if somewhat derivative, film proved to be a box office hit. Kleiser followed with "The Blue Lagoon" (1980), starring Brooke Shields and Christopher Atkins. Despite its rather trite story, it, too, proved to be a success at the box office. Gorgeously shot by cinematographer Nestor Almendros, "The Blue Lagoon" was a cool film, in part due to Kleiser's direction of the slightly improbable material. Audiences went to the film to see its stars cavorting in the sun and sand.

After his big screen successes, Kleiser hit a lull with such forgettable efforts as "Grandview USA" (1984) and "Flight of the Navigator" (1986). The quirky sequel, "Big Top Pee-wee" (1988), had some comic moments, but, overall, was not as popular as the other Paul Reubens' big-screen effort. By the 1990s, Kleiser's feature film work perked up. "White Fang" (1991) was well-received by critics and the sequel "Honey, I Blew Up the Kid" (1992) won a modest box office. But "Return to the Blue Lagoon" (1991) failed to duplicate the spirit or success of its original.

The openly gay Kleiser chose to film a far more personal project, based upon his relationship with his lover who, suffering from complications from AIDS, chose to end his life. The result was "It's My Party" (1996), starring Eric Roberts, Gregory Harrison, Bronson Pinchot, Margaret Cho, and Olivia Newton-John, was well-received at several film festivals, including Sundance.