Peter Orlovsky was born in 1933 to Oleg, a Russian immigrant who painted silk neckties and Katherine Orlovsky, an aspiring writer. He was born in Manhattan, on the Lower East Side, but grew up on Long Island in the town of Northport. The family was poor and both Oleg and Katherine were alcoholics and the Orlovsky's five children were often neglected and abused. The oldest son, Julius, went mad and had, eventually to be institutionalized, and both Peter and his younger brother Lafcadio struggled throughout their lives with substance abuse.

Peter, the second of the Orlovsky's five children left his mother's home at 17. He worked as an orderly in a mental hospital in Queens while taking night classes to complete the requirements for his high school diploma. In 1953 he was drafted into the Korean war where he served as a medic in a hospital in San Francisco.

In 1954, Orlovsky and moved in with painter Robert LaVigne acting both as the painter's model and his lover. Through LaVigne he met other writers and artists, most significantly Allen Ginsberg. Orlovsky and Ginsberg almost immediately became lovers and within months entered into a marriage that would last most of the remainder of their lives.

Ginsberg and Orlovsky lived together first in North Beach in California and later in New York City, but also traveled extensively throughout Europe and the Mediterranean as well as India and Pakistan. Though he lived and traveled all over the globe, Peter felt his responsibility to his brothers Julius and Lafcadio keenly, and his trips abroad were often abbreviated in order for him to care for one or both of them.

With Ginsberg's influence and encouragement, Orlovsky began writing poetry in 1957 while the two were living in Paris. He was first published in 1960 and continued to write throughout that decade, though this is also when his own drug use, particularly amphetamines, was at its worst.

In 1970 Orlovsky moved to the farm Allen Ginsberg purchased in Cherry Valley, New York to pursue organic farming and his writing. He joined the faculty of the Jack Kerouac School of Disembodied Poetics at the Naropa Institute in 1974 to teach the course "Poetry for Dumb Students" and remained a core member of the faculty for several years. He was awarded a $10,000 National Endowment for the Arts grant in 1979.

He is the author of several books of poetry including Dear Allen: Ship will land Jan 23, 58, Clean Asshole Poems & Smiling Vegetable Songs: Poems 1957-1977, Lepers Cry, and the volume Straight Hearts' Delight--Love Poems and Selected Letters, by Orlovsky and Allen Ginsberg as well as publishing poems in a number of periodicals. He was also featured in Robert Frank's documentary film Me and My Brother (1969), which explores Julius Orlovsky's mental illness.