Pirsig was born and raised in Minneapolis, Minnesota to Maynard E. Pirsig and Harriet Marie Sjobeck, and is of German and Swedish descent. His father was a University of Minnesota Law School (UMLS) graduate, and started teaching at the school in 1934. The elder Pirsig served as the law school dean from 1948 to 1955, and retired from teaching at UMLS in 1970. He resumed his career as a professor at the William Mitchell College of Law, where he remained until his final retirement in 1993.

Because he was a precocious child, with an I.Q. of 170 at age 9, Robert Pirsig skipped several grades and was enrolled at the Blake School in Minneapolis. Pirsig was granted a high school diploma in May 1943, and entered the University of Minnesota to study biochemistry that autumn. In Zen and the Art of Motorcycle Maintenance, he described the central character, thought to represent himself, as being far from a typical student; he was interested in science as a goal in itself, rather than as a way to establish a career.

While performing biochemical laboratory work, Pirsig was greatly troubled by the theory that there is always more than one workable hypothesis to explain a given phenomenon, and that the number of hypotheses appeared unlimited. He could not search for any way around this, and to him it seemed that the whole scientific endeavor had been ceased. The question distracted him to the extent that he was expelled from the university, due primarily to failing grades and lack of interest in his studies.

Pirsig enlisted in the United States Army in 1946, and was stationed in South Korea for two years until 1948. He was returned to the United States upon discharge, and briefly resided in Seattle, Washington for less than a year, until he decided to finish post-secondary education he abandoned; he earned a Bachelor of Arts in Eastern Philosophy in May 1950. He then attended Banaras Hindu University in India, to further study Eastern Philosophy and culture. Although he was not granted a degree, he performed graduate-level work in philosophy and journalism at the University of Chicago. His difficult experiences as a student in a course taught by Richard McKeon were later described, thinly disguised, in Zen and the Art of Motorcycle Maintenance. In 1958, he became a professor at Montana State University in Bozeman, and taught creative writing courses for two years.

Due to suffering a nervous breakdown, Pirsig spent time in and out of psychiatric hospitals between 1961 to 1963. He was diagnosed with paranoid schizophrenia and clinical depression as a result of an evaluation conducted by psychoanalysts, and was treated with shock therapy on numerous occasions.

In years following the publication of Zen and the Art of Motorcycle Maintenance, he has lived a solitary and reclusive lifestyle. Pirsig has travelled around the Atlantic by boat, and has resided in Norway, Sweden, Belgium, Ireland, England and in various places around the United States since 1980.

Robert Pirsig married Nancy Ann James on May 10, 1954. They had two sons: Chris, born in 1956, and Theodore, born in 1958. After Pirsig was first hospitalized in 1961, James filed for divorce, which was finalized in 1978. Shortly after, he married Wendy Kimball on December 31, 1978.

In 1979, Pirsig's son Chris, who figured prominently in Zen and the Art of Motorcycle Maintenance, was stabbed to death during a mugging outside the San Francisco Zen Center. Pirsig discusses this incident in an afterword to subsequent editions of Zen and the Art of Motorcycle Maintenance, writing that he and his second spouse, Kimball, decided not to abort the child she conceived in 1980, because he had come to believe that this unborn child was a continuation of the life pattern that Chris had occupied. This child's name is Nell, and she is Pirsig's daughter.

Pirsig's work consists almost entirely of two novels. Zen and the Art of Motorcycle Maintenance sets out Pirsig's interpretation of "Quality" and "the Good." It is mostly a first person narrative based on a motorcycle trip he and his young son Chris took from Minneapolis to San Francisco.

Pirsig's publisher's recommendation to his Board ended with "This book is brilliant beyond belief, it is probably a work of genius, and will, I'll wager, attain classic stature." Pirsig noted in an early interview, that Zen was rejected 121 times before being accepted by William Morrow Publishers. In his book review, George Steiner compared Pirsig's writing to Dostoevsky, Broch, Proust, and Bergson, stating that "the assertion itself is valid... the analogies with Moby-Dick are patent". The Times Literary Supplement called it "Profoundly important, Disturbing, Deeply moving, Full of insights, A wonderful book".

In 1974, Pirsig was awarded a Guggenheim Fellowship to allow him to write a follow-up, An Inquiry into Morals (1991), in which he elaborates and focuses on a value-based metaphysics, called Metaphysics of Quality, to replace the subject-object view of reality.