Born Robert Sanders in Kansas City, Missouri on January 14, 1933, Brakhage was adopted and renamed three weeks after his birth by Ludwig and Clara Brakhage.

Brakhage briefly attended Dartmouth College on a scholarship before dropping out to make films. He completed his first film, Interim, at the age of 19; the music for the film was composed by his school friend James Tenney. In 1953, Brakhage moved to San Francisco to attend the San Francisco Art Institute, then called the California School of the Arts. He found the atmosphere in San Francisco more rewarding, associating with poets Robert Duncan and Kenneth Rexroth, but did not complete his education, instead moving to New York City in 1954. There he met a number of notable artists, including Maya Deren (in whose apartment he briefly lived), Willard Maas, Jonas Mekas, Marie Menken, Joseph Cornell, and John Cage. Brakhage would collaborate with the latter two, making two films with Cornell (Gnir Rednow and Centuries of June) and using Cage’s music for the soundtrack of his first color film, In Between. Brakhage is recorded to have said “If there is one single filmmaker that I owe the most to for the crucial development of my own film making it would be Marie Menken.”

Brakhage spent the next few years living in near poverty, depressed about what he saw as the failure of his work. He briefly considered suicide. While living in Denver, Brakhage met Mary Jane Collom (see Jane Wodening), whom he married in late 1957. Brakhage tried to make money on his films, but had to take a job making industrial shorts to support his family. In 1958, Jane gave birth to the first of the five children they would have together, a daughter called Myrrena, an event Brakhage recorded for his 1959 film Window Water Baby Moving.

From 1961 to 1964, Brakhage worked on a series of five films known as the Dog Star Man cycle. The Brakhages moved to Lump Gulch, Colorado, in 1964, though Brakhage continued to make regular visits to New York. During one of those visits, the 16mm film equipment he had been using was stolen. Brakhage couldn’t afford to replace it, instead opting to buy cheaper 8mm film equipment. He soon began working in the format, producing a 30-part cycle of 8mm films known as the Songs from 1964 to 1969. The Songs include one of Brakhage’s most acclaimed films, 23rd Psalm Branch, a response to the Vietnam War and its presentation in the mass media.

In 1961, Jonas Mekas wrote that Brakhage is “one of the four or five most authentic film artists working in cinema anywhere, and perhaps the most original filmmaker in America today”, Among Brakhage’s students were Eric Darnell, the director of Antz, as well as the creators of South Park, Matt Stone and Trey Parker, and he is featured in their student film Cannibal! The Musical.

When Brakhage’s early films had been exhibited in the 1950s, they had often been met with derision, but in the early 1960s Brakhage began to receive recognition in exhibitions and film publications, including Film Culture, which gave awards to several of his films, including The Dead, in 1962. The award statement, written by Jonas Mekas, a critic who would later become an influential experimental filmmaker in his own right, cited Brakhage for bringing to cinema “an intelligence and subtlety that is usually the province of the older arts.” Writer/critic Guy Davenport, an ardent admirer of Brakhage, invited him to the University of Kentucky in March 1964 and tried to get him a residency there.

Brakhage began teaching film history and aesthetics at the School of the Art Institute of Chicago in 1969, commuting from his home in Colorado.

Brakhage explored new approaches to filmmaking in the 1970s. In 1971, he completed a set of three films inspired by public institutions in the city of Pittsburgh. These three films–Eyes, about the city police, Deus Ex, filmed in a hospital, and The Act of Seeing with One’s Own Eyes, depicting autopsy—are collectively known as “The Pittsburgh Trilogy”. In 1974, Brakhage made the feature-length The Text of Light, consisting entirely of images of light refracted in a glass ashtray. In 1979, he experimented with Polavision, a format marketed by Polaroid, making about five 2⁄2 minute films. The whereabouts of these films are now unknown. He continued his visual explorations of landscape and the nature of light and thought process, and through the late 1970s and early 1980s produced filmic equivalents of what he termed “moving visual thinking” in several series of photographic abstractions known as the Roman, Arabic, and Egyptian series.

Stan Brakhage taught at the University of Colorado in Boulder off and on, in the late 1970s and early 1980s. He separated from Jane in 1986, and in 1989 married his second wife, Marilyn; the two went on to have two children together. In the late 1980s, Brakhage returned to making sound films, with the four-part Faustfilm cycle, and also completed the hand-painted film, The Dante Quartet.

Brakhage was awarded the Edward MacDowell Medal in 1989.

Brakhage was diagnosed with bladder cancer in 1996, and his bladder was removed. The surgery seemed successful, but the cancer eventually returned. In a video interview in 2002, he explained that his cancer was caused by the toxicity of the aniline dyes he had used to paint directly onto film.

Brakhage retired from teaching and moved to Canada in 2002, settling with his second wife Marilyn and their two sons in Victoria, British Columbia. Brakhage died there on March 9, 2003, aged 70. The last footage Brakhage shot has been made available under the title Work in Progress. At the time of his death, Brakhage was also working on the Chinese Series, a work that was achieved by means he had utilized in the past scratching directly on to film, a technique that was employed by the French artist Isou in 1950.

The 2011 film The Tree of Life and Part 8 of Twin Peaks: The Return (2017) include sequences reminiscent of Brakhage’s work.