Crosby has been inducted into the Rock and Roll Hall of Fame twice: once for his work in The Byrds and once for his work with CSN. Five albums he contributed to are included in Rolling Stone's 500 Greatest Albums of All Time, three with the Byrds and two with CSN(Y). He is outspoken politically and has been depicted as emblematic of the 1960s' counterculture.

Crosby had a biological son, James Raymond, in 1962, who was placed for adoption and reunited with Crosby as an adult. Since 1997, Raymond has performed with Crosby on stage and in the studio, as a member of CPR and as part of the touring bands for Crosby & Nash and Crosby, Stills & Nash. In addition, Crosby has three other children: a daughter, Erika, with Jackie Guthrie, a daughter, Donovan Crosby, with former girlfriend Debbie Donovan and a son, Django Crosby, who was conceived with wife Jan Dance after extensive fertility treatments while Crosby's liver was failing.

Crosby arrived back in Chicago from NYC to hang out with Terry Callier. On tour and in Chicago at that time was Miriam Makeba and her band, which included a multi intrumentalist Jim McGuinn. Terry introduced McGuinn to Crosby. Crosby joined Jim McGuinn (who later changed his name to Roger) and Gene Clark, who were then named the Jet Set. They were augmented by Drummer Michael Clarke, at which point Crosby attempted, unsuccessfully, to play bass. Late in 1964, Chris Hillman joined as Bassist, and Crosby relieved Gene Clark of rhythm guitar duties. Through connections that Jim Dickson (the Byrds' manager) had with Bob Dylan's publisher, the band obtained a demo acetate disc of Dylan's "Mr. Tambourine Man" and recorded a version of the song, featuring McGuinn's 12-string guitar as well as McGuinn, Crosby, and Clark's vocal harmonizing. The song turned into a massive hit, reaching number one in the charts in the United States and the United Kingdom during 1965. While McGuinn originated the Byrds' trademark 12-string guitar sound, Crosby was responsible for the soaring harmonies and often unusual phrasing of their songs, but whilst he didn't sing lead vocals on either of the first two albums, he sang lead on the bridge in their second single "All I Really Want to Do."

In 1966, Gene Clark, who then was the band's primary Songwriter, left the group because of stress and this placed all the group's songwriting responsibilities in the hands of McGuinn, Crosby, and Hillman. Crosby took the opportunity to hone his craft and soon became a relatively prolific Songwriter, collaborating with McGuinn on the uptempo "I See You" (covered by Yes on their 1969 debut) and penning the ruminative "What's Happening". His early Byrds efforts also included the 1966 hit "Eight Miles High" (to which he contributed one line, while Clark and McGuinn wrote the rest), and its flip side "Why," co-written with McGuinn.

Friction between Crosby and the other Byrds came to a head in mid-1967. Tensions were high after the Monterey Pop Festival in June, when Crosby's onstage political diatribes (including a frank discussion of the John F. Kennedy assassination conspiracy theories) between songs elicited rancor from McGuinn and Hillman. He further annoyed his bandmates when, at the invitation of Stephen Stills, he substituted for an absent Neil Young during Buffalo Springfield's set the following night. The internal conflict boiled over during the initial recording sessions for The Notorious Byrd Brothers (1968) that summer, where differences over song selections led to intra-band arguments. In particular, Crosby was Adam Ant that the band should record only original material despite the recent commercial failure of "Lady Friend", a Crosby-penned single that stalled at No. 82 on the American charts following its release in July. McGuinn and Hillman dismissed Crosby in October after he refused to countenance the recording of a cover of Goffin and King's "Goin' Back". While Crosby contributed to three compositions and five recordings on the final album, his controversial menage-a-trois ode "Triad" was omitted. Jefferson Airplane released a Grace Slick-sung cover on Crown of Creation (1968); three years later, Crosby released a solo acoustic version on Crosby, Stills, Nash and Young's double live album Four Way Street (1971). The Byrds' version appeared decades later on the 1988 Never Before release and is now available on the CD re-release of The Notorious Byrd Brothers.

Around the time of Crosby's departure from the Byrds, he met a recently unemployed Stephen Stills at a party at the home of Cass Elliot (of the Mamas and the Papas) in California in March 1968, and the two started meeting informally and jamming together. They were soon joined by Graham Nash, who would leave his commercially successful group the Hollies to play with Crosby and Stills. Their appearance at the Woodstock Music and Art Fair in August 1969 constituted their second live performance ever.

In 1969, Neil Young joined the group, and with him they recorded the album Déjà Vu, which peaked at number 1 on the Billboard 200 and the ARIA Charts. That same year, Crosby's longtime girlfriend Christine Hinton was killed in a car accident only days after Hinton, Crosby, and Debbie Donovan moved from Los Angeles to the Bay Area. Crosby was devastated, and he began abusing drugs more severely than he had before. Nevertheless, he still managed to contribute "Almost Cut My Hair" and the title track "Déjà Vu". After the release of the double live album Four Way Street, the group went on a temporary hiatus to focus on their respective solo careers.

In December 1969, Crosby appeared with CSNY at the Altamont Free Concert, increasing his visibility after also having performed at Monterey Pop and Woodstock. At the beginning of 1970, he briefly joined with Jerry Garcia, Phil Lesh and Mickey Hart from Grateful Dead, billed as "David and the Dorks", and making a live recording at the Matrix on December 15, 1970.

Renewing his ties to the San Francisco milieu that had abetted so well on his solo album, Crosby sang backup vocals on several Paul Kantner and Grace Slick albums from 1971 through 1974 and the Hot Tuna album Burgers in 1972. He also participated in Composer Ned Lagin's proto-ambient project Seastones along with members of the Grateful Dead and Jefferson Starship.

CSNY reunited in the summer of 1973 for unsuccessful recording sessions in Maui and Los Angeles. Despite lingering acrimony, they reconvened at a Stills concert at the Winterland Ballroom in San Francisco in October. This served as a prelude to their highly successful stadium tour in the summer of 1974. Following the tour, the foursome attempted once again to record a new album, provisionally entitled Human Highway. The recording sessions, which took place at The Record Plant in Sausalito, were very unpleasant, marked by constant bickering. The bickering eventually became too much, and the album was canceled.

In rehearsals for the 1974 tour, CSNY recorded a then-unreleased Crosby song, "Little Blind Fish". A different version of the song would appear on the second CPR album more than two decades later. The 1974 tour was also full of constant bickering, though they managed to finish it without interruption. A greatest hits compilation entitled So Far was released during 1974 to capitalize on the foursome's reunion tour.

In 1976, as separate duos, Crosby & Nash and Stills & Young were both working on respective albums and contemplated retooling their work to produce a CSNY album. This attempt ended bitterly as Stills and Young deleted Crosby and Nash's vocals from their album Long May You Run.

Crosby worked with Phil Collins occasionally from the late 1980s to the early 1990s. He sang backup to Collins in "That's Just the Way It Is" and "Another Day in Paradise", and, on his own 1993 song, "Hero", from his album Thousand Roads, Collins sang backup. In 1992, Crosby sang backup on the album Rites of Passage with the Indigo Girls on tracks 2 and 12. In 1999, he appeared on Return of the Grievous Angel: A Tribute to Gram Parsons, singing a duet of the title track with Lucinda Williams.

In 1982, after being convicted of several drugs and weapons offenses, Crosby spent nine months in a Texas state prison. The drug charges stemmed from charges related to possession of heroin and cocaine.

In 1985, Crosby was arrested for drunken driving, a hit-and-run driving accident, and possession of a concealed pistol and drug paraphernalia. Crosby was arrested after driving into a fence in a Marin County suburb, where officers found a .45-caliber pistol and cocaine in his car.

During the early 1990s, Crosby appeared as a guest star in several episodes of The John Larroquette Show, where he played the part of Larroquette's AA sponsor. He appeared on an episode of Roseanne as the singer–husband of one of Roseanne's co-workers, who was played by Bonnie Bramlett. He sang the Danny Sheridan composition "Roll On Down" on that episode. He was on an episode of Ellen called "Ellen Unplugged", in which he was helping out at the Rock and Roll Fantasy Camp. He also appeared as a pirate in the 1991 film Hook, as a 1970s hippie in the 1991 film Backdraft, and as a bartender in the 1992 feature film Thunderheart.

Crosby was the recipient of a highly publicized liver transplant in 1994, which was paid for by Phil Collins. News of his transplant created some controversy because of his Celebrity status and his past problems with drug and alcohol addiction. Crosby's liver problems stemmed from a long run with hepatitis C.

In 1996, Crosby formed CPR or Crosby, Pevar & Raymond with session Guitarist Jeff Pevar, and Pianist James Raymond, Crosby's son. The group released two studio albums and two live albums before disbanding in 2004.

Crosby's brother Ethan, who taught him to play guitar and started his musical career with him, committed suicide in late 1997 or early 1998; the date is unknown because Ethan left a note not to search for his body but to let him return to the earth. His body was found months later in May 1998.

In January 2000, Melissa Etheridge announced that Crosby was the biological father of two children with her then lesbian partner Julie Cypher by means of artificial insemination. At the time, Etheridge and Cypher were still in a relationship.

On March 7, 2004, Crosby was charged with Criminal possession of a weapon in the third degree, illegal possession of a hunting knife, illegal possession of ammunition, and illegal possession of about one ounce of marijuana. Crosby left said items behind in his hotel room. Authorities said a "hotel employee searched the suitcase for identification and found about an ounce of marijuana, rolling papers, two knives and a .45-caliber pistol. Mr. Crosby was arrested when he returned to the hotel to pick up his bag." After spending 12 hours in jail, he was released on $3,500 bail. On July 4, 2004, he pleaded guilty to attempted Criminal possession of a weapon, was fined $5,000 and given no jail time. Prosecutors did not seek a more severe penalty on the weapons charge because the pistol was registered in California and was stowed safely in his luggage when it was found. A charge of unlawful possession of marijuana was dismissed. Crosby was discharged by the court on condition that he pay his fine and not get arrested again.

In 2006, Crosby and Nash worked with David Gilmour as backing vocalists on the latter's third solo album, On an Island. The album was released in March 2006 and reached number 1 on the UK charts. They also performed live with Gilmour in his concert at the Royal Albert Hall in London in May 2006 and toured together in the United States, which can be seen on Gilmour's 2007 DVD Remember That Night.

Crosby suffers from type 2 diabetes and is being treated with insulin to manage the disease. At a concert in October 2008, Crosby, looking quite thinner than in recent years, announced to the audience that he had recently shed 55 pounds as a result of his struggles with the disease.

Following up on a transformative sailing experience when he was 11, Crosby purchased a 59-foot, John Alden–designed schooner named Mayan with his Byrds settlement. In the decades before he sold the boat in 2014, Crosby sailed it thousands of miles in the Pacific and Caribbean. He has credited the Mayan as being a songwriting muse; he wrote some of his best-known songs aboard the boat, including "Wooden Ships," "The Lee Shore," "Page 43," and "Carry Me."

In February 2014, at the urging of his Doctor, Crosby postponed the final dates of his solo tour in order to undergo a cardiac catheterization and angiogram, based on the results of a routine cardiac stress test.

On August 26, 2016, David Crosby announced a U.S. tour behind his upcoming fifth solo LP, a 18-date trek due to launch on November 18, 2016 in Atlanta, Georgia and to conclude on December 16, 2016 in Ithaca, New York.

In September 2017, David Crosby announced a new solo album (his third one of original material in four years and his sixth one in total) entitled Sky Trails due to be released on September 29, 2017 on BMG.