In 1974, Mansfield formed the Christian country rock band, Jubal, along with Don Gerber, Paul Angers, Steve Kara, and Henry Cutrona.After a name change from Jubal to Gentle Faith, the group released their self-titled album, Gentle Faith, in 1976.

In 1977, Mansfield formed the Darrell Mansfield Band. He has since recorded over 30 albums and toured throughout the United States, Europe, the Middle East, Asia, and Australia.

Mansfield has contributed vocals and harmonica to recordings by artists including Adam Again, Eddie Van Halen, Jon Bon Jovi, Loverboy, and Raphael Saadiq. He has also played alongside Billy Idol, Billy Sheehan, Earl Slick, Glenn Kaiser, Jimmy Hall, Joe Turner, Richie Sambora, Rick Derringer, Ted Nugent, and The Blind Boys of Alabama.

Mansfield was inducted into the Hohner Harmonica Hall of Fame in 1980 and is the "Ambassador to California" for the Blues Hall of Fame.

Mansfield is a vocal advocate for those facing mental health issues. Having struggled with depression throughout his life as a result of a chemical imbalance, Mansfield attempted suicide on numerous occasions, first in 1971, and later spent two years at Atascadero State Hospital in central California.He now incorporates the discussion of mental health in his music ministry.