Born in Kansas City, Missouri, Basil Poledouris credited two influences with guiding him towards music: the first was composer Miklós Rózsa, the second was his Greek Orthodox heritage. Poledouris was raised in the church, and used to sit in services, enthralled with the choir's sound. At age 7 he began piano lessons, and eventually enrolled at the University of Southern California to study both film and music. Several short films to which he contributed still reside in the university's archives. At USC he met directors John Milius and Randal Kleiser, with both of whom the composer would later collaborate. In 1985, he scored Flesh & Blood for director Paul Verhoeven, again establishing another ongoing collaboration.

Poledouris became renowned for his powerfully epic style of orchestral composition and his intricate thematic designs, and garnered attention for his scores to The Blue Lagoon (1980, dir: Kleiser), Conan the Barbarian (1982, dir: Milius), Conan the Destroyer (1984), Red Dawn (1984, dir: Milius), RoboCop (1987, dir: Verhoeven), The Hunt for Red October (1990), Free Willy (1993) and its sequels, Starship Troopers (1997, dir: Verhoeven) and For Love of the Game (1999).

Poledouris married his wife, Bobbie, in 1969 and had two daughters, Zoë and Alexis. The elder, Zoë Poledouris, is an actress and film composer who occasionally collaborated with her father composing film soundtracks.

His score for Conan the Barbarian is considered by many to be one of the finest examples of motion picture scoring ever written.

He spent the last four years of his life living on Vashon Island, in Washington state, and died on November 8, 2006 in Los Angeles, California, aged 61, due to complications from cancer.