Born in West Virginia and raised in Detroit, Sampedro moved to California as soon as he was old enough to drive. Having spent the next few years playing in different bands, Sampedro joined Crazy Horse in 1975 to record Zuma, after being introduced to the band by Billy Talbot in November 1974, exactly two years after the death of original Crazy Horse guitarist Danny Whitten.
With the addition of Sampedro on rhythm guitar, Crazy Horse developed a new, rigid sound (as opposed to the more free-form approach of the Whitten era) that served as a seminal influence in the development of grunge and noise rock while also enabling Neil Young to focus more on his lead playing. Although Crazy Horse did not work with Young for much of the 1980s, Sampedro remained an integral part of Young's circle throughout the epoch, playing on several solo albums (most notably Freedom) and tours; his proficiency in emerging computer technology allowed him to cultivate a second career with the Young organization that would blossom in the years thereafter.
For many years, he worked as an engineer on The Tonight Show with Jay Leno under bandleader Kevin Eubanks, running the ensemble's MIDI board. Sampedro retired from the program in 2010 to raise fruit (including bananas, mangoes, pineapples and papayas).
As a member of Crazy Horse:
- Crazy Moon (1978)
- Gone Dead Train: The Best of Crazy Horse 1971-1989 (2005)
- Scratchy: The Complete Reprise Recordings (2005)
As a member of Neil Young & Crazy Horse:
- Zuma (1975)
- Rust Never Sleeps (1979)
- Live Rust (live, 1979)
- Re·ac·tor (1981)
- Life (1987)
- Ragged Glory (1990)
- Arc/Weld (live, 1991)
- Sleeps With Angels (1994)
- Broken Arrow (1996)
- Year of the Horse (live, 1997)
- Americana (2012)
- Psychedelic Pill (2012)
Contributions to other Neil Young albums:
- American Stars 'N Bars (1977)
- Comes A Time (1978)
- Trans (1982)
- This Note's For You (1988)
- Freedom (1989)
- Are You Passionate? (2002)
- Chrome Dreams II (2007)
Contributions to records by other artists:
- Glimmer, Kevin Salem's second solo album from 1996 (guitar);
- Harlem, a Shawn Amos album released in 2000 (guitar).
- An interview with Frank Sampedro during Greendale tour in Australia: http://www.undercover.com.au/idol/crazyhorse.html
- Another interview from 1996: http://www.thrasherswheat.org/yoth/pancho110196.htm