Sampedro joined Neil Young and Crazy Horse in 1975 to record
Zuma. He was introduced to the band by bassist/vocalist
Billy Talbot in November 1974 during aborted sessions at
Chess Studios in
Chicago, exactly two years after the death of original Crazy Horse second guitarist
Danny Whitten. Talbot and Sampedro had initially befriended each other at the house of actress
June Fairchild in late 1973 or early 1974. Shortly thereafter, Talbot accompanied Sampedro to
Ensenada, Baja California, where the latter was temporarily relocating due to a legal matter. As they "jammed on the beach with a couple of acoustic guitars," Talbot realized that "[Sampedro] was the guy we could use." With the addition of Sampedro on
rhythm guitar, Crazy Horse developed a new, streamlined
hard rock sound (as opposed to the interwoven, free-form approach of the Whitten era) that served as a seminal influence in the development of
grunge and
noise rock while also enabling Young to focus more on his lead playing. Although Sampedro lacked Whitten's instrumental proficiency at this juncture (leading Young to simplify his writing for the group and initially inspiring skepticism from drummer
Ralph Molina), Young would later opine that "Poncho was a resource to be reckoned with. He made it possible to play with the Horse." Sampedro brought a rawer edge to Crazy Horse, and not just musically. "Rock 'n' roll—I thought that meant loot the village and rape the women," recalled Sampedro. Much to the consternation of Young, Sampedro frequently used
heroin in his early days with the band, leading Young to once jump out of their car in Europe when he realized that Sampedro was procuring the drug. On a 1976 tour of Europe and Japan, Sampedro and Talbot took
LSD before stepping onstage at the
Budokan in
Tokyo. "I'd hit the strings of my guitar—they were like eighty different colors—and they bounced off the floors and hit the ceiling," Sampedro later recalled. According to Young, he and Sampedro did "a lot of illegal things" during this period. Despite occasional tumult stemming from Young's signature mutability, the Sampedro version of Crazy Horse would contribute to Young's next two albums and served as the backing band for his 1979 album/concert film
Rust Never Sleeps. In November 1978, Crazy Horse also released
Crazy Moon, their fourth non-Young album; six of the album's eleven songs were written or co-written by Sampedro. Throughout the 1980s, the band also contributed to Young's
Re-ac-tor (1981),
Trans (1982) and
Life (1987). As Young moved on to other projects and other bands in the late eighties, Sampedro remained in his employ even as Talbot and Molina released a non-Young Crazy Horse album without Sampedro in 1989. His importance to Young's work at the time was such that Young's co-producer
Niko Bolas stated, "You can't do a Neil Young album without Poncho...there's no one thing he does, but if he wasn't there it'd come apart." As a member of The Bluenotes (a horn-driven
blues rock ensemble later rechristened Ten Men Workin'), Sampedro played on Young's ''
This Note's for You'' (1988) and contributed keyboards and guitar to the band's ensuing support tour; a selection of live recordings from the Bluenotes era were finally released as
Bluenote Café in 2015. Although he was not included in The Restless (a short-lived hard rock
power trio that evolved from Ten Men Workin'), Sampedro contributed heavily to Young's 1989 album,
Freedom. Sampedro also received a belated co-writing credit on the Young anthem "Rockin' in the Free World." He explained in a 2013
Rolling Stone interview that in 1989 Young and Crazy Horse were scheduled to perform in Russia but the performances were canceled. Sampedro told Young, "I guess we'll have to keep on rockin' in the free world," to which Young replied, "Wow, that's a cool line. That's a really good phrase. I wanna use it." On the September 30, 1989 broadcast of
Saturday Night Live, Sampedro led an ad hoc ensemble (including drummer
Steve Jordan and bassist
Charley Drayton) that backed Young for "No More" and "Rockin' in the Free World", regarded by critics as one of the greatest live rock television performances of all time. (The band, said one writer, looked like "a bunch of car thieves.") Sampedro also accompanied Young on mandolin and piano on the subsequent solo tour. In 1990, Crazy Horse (once again including Sampedro) returned for Young's 1990 album
Ragged Glory and two live albums recorded on the following tour,
Weld and
Arc. Young then used Crazy Horse for
Sleeps with Angels (1994) and
Broken Arrow (1996). Sampedro's proficiency in emergent computer technology (honed during Young's experiments with the medium in the early 1980s) allowed him to cultivate another career. He worked as an engineer on
The Tonight Show with Jay Leno from 1992 to 2010 under bandleader
Kevin Eubanks, running the ensemble's
MIDI board as well as serving as an assistant/project manager to Eubanks. In 1997, Crazy Horse was featured on Young's live
Year of the Horse album. Sampedro's appearance in
Jim Jarmusch's accompanying documentary led
San Francisco Examiner critic Craig Marine to state "the funniest parts of the movie are when guitarist Frank 'Poncho' Sampedro repeatedly berates the director. Sampedro accuses Jarmusch of trying to make 'an artsy-fartsy film' to try to look cool and 'impress his New York friends'." Sampedro sat out the Neil Young and Crazy Horse-recorded
Greendale in 2003 but returned for the tour.
Trick Horse, a collection of previously unreleased non-Young Crazy Horse recordings pseudonymously produced by Sampedro as "Poncho Villa", was released on iTunes in 2009. Following an extended hiatus, Sampedro and his bandmates rejoined Young for an eccentric album of covers (
Americana) and an album of original material (
Psychedelic Pill) before touring intermittently for two years. In 2021, for the release of
Way Down in the Rust Bucket, Sampedro was given joint credit on writing "Surfer Joe and Moe the Sleaze" (originally on
Re-ac-tor) and "Fuckin' Up" (on
Ragged Glory), two songs previously only credited to Young. ==Retirement from touring and recording==