During their formative years, the band was composed of Bruce Hampton, Oteil Burbridge, Jimmy Herring, Jeff Sipe, Matt Mundy, and Count M'Butu.

This lineup produced two albums released on Capricorn Records; Col. Bruce Hampton and the Aquarium Rescue Unit, in 1992,[3] and Mirrors of Embarrassment, in 1993.

Also, in 1992 Billy Bob Thornton directed the movie Widespread Panic: Live from the Georgia Theatre which features a music video for "Basically Frightened" performed by Col. Bruce Hampton & The Aquarium Rescue Unit with Chuck Leavell and Count M'Butu.

The band had a rotating outer cast of members over the years, including lead vocalist Paul Henson; Oteil's brother, Kofi Burbridge on keyboards, flute, back-up vocals; and drummer Sean O'Rourke.

Jeff Sipe joined with Jonas Hellborg and the late Shawn Lane in 1995, and over the years has played with Leftover Salmon, Susan Tedeschi, Phil Lesh, and Trey Anastasio.

He was asked to fill the bass slot in the post-Fare Thee Well incarnation of The Grateful Dead when Phil Lesh decided he no longer wanted to tour.

Bobby Lee Rodgers of The Codetalkers was asked to sit in on banjo and vocals, taking the place of Matt Mundy who has retired from performing.