Persky was born in Chicago, Illinois. As a teenager, he made contact with and received encouragement from Jack Kerouac, Allen Ginsberg and other writers of the Beat Generation. Persky served in the United States Navy, and then settled in San Francisco, California in the early 1960s, becoming part of a group of writers that included Jack Spicer, Robert Duncan, Robin Blaser and George Stanley.

In 1966, Persky moved to Vancouver, Canada, and attended the University of British Columbia, receiving degrees in anthropology and sociology. He studied with anthropologist Michael Kew, political philosopher Bob Rowan, and sociologist Roy Turner, and briefly studied as a graduate student with Rowan's teacher, political philosopher Joseph Tussman in the Experimental Program at the University of California, Berkeley. He became a Canadian citizen in 1972. During the 1960s and '70s, he was prominent as a student and civic activist, was an early staff member of the Georgia Straight, a free alternative newspaper, and co-founder with Dennis Wheeler of the "Georgia Straight Writing Supplement," which eventually became New Star Books.

After university, Persky worked at Vancouver Mental Patients Association and the Canadian Broadcasting Corporation before becoming a college instructor in the sociology department at Northwest College in Terrace, British Columbia. He subsequently taught briefly at Malaspina College in Nanaimo, British Columbia and Simon Fraser University in Burnaby. Since 1983, he has worked primarily at Capilano University in North Vancouver, first in political studies and then in philosophy. Since 1990, Persky has resided part-time in Vancouver and in Berlin, Germany.

He worked as a media commentator for the CBC, a literary columnist for The Globe and Mail and The Vancouver Sun, and has written for The Body Politic, This Magazine, New Directions, Saturday Night, Sodomite Invasion Review, Books in Canada and most recently The Tyee. He is also a frequent contributor to Dooney's Cafe. Stan Persky is a long-time Vancouver public intellectual and literary activist. His most recent publication, co-authored with Brian Fawcett, is Robin Blaser, a memorial book about the Vancouver poet.