Over the years, artists who recorded at Muscle Shoals Sound Studio included Bob Dylan, The Rolling Stones, Aretha Franklin, Wilson Pickett, Willie Nelson, Duane Allman, Lynyrd Skynyrd, Joe Cocker, Levon Helm, Paul Simon, Bob Seger, Rod Stewart, Cat Stevens, Cher, George Michael, and The Black Keys.

The four founders of the studio, Barry Beckett, Roger Hawkins, Jimmy Johnson and David Hood, were session musicians at Rick Hall's FAME Studios; they were officially known as the Muscle Shoals Rhythm Section but widely referred to as "The Swampers,"[3] who were recognized as having crafted the "Muscle Shoals sound" in conjunction with Hall.

Their initial successes in soul and R&B led to more mainstream rock and pop performers who began coming to record at Muscle Shoals Sound Studios, including the Rolling Stones, Bob Dylan, Duane Allman, Traffic, Bob Seger, Glenn Frey, Elton John, Paul Simon, Boz Scaggs, Willie Nelson, Dr. Hook, Elkie Brooks, Millie Jackson, and Julian Lennon.

This location operated until it was closed and sold in 1985 to Malaco Records, Tommy Couch's Jackson, Mississippi-based soul and blues label, which also bought the publishing rights held by the Muscle Shoals Sound.

Malaco used the Sheffield studios for its own artists, including Johnnie Taylor, Bobby Bland and Little Milton, while continuing to operate its original facility in Jackson.

Band of Horses's third CD, Infinite Arms, recorded in part at that studio, was nominated for a Grammy Award in the category Best Alternative Album.

The original studio building on Jackson Highway, which had become an audio visual retailer and then an appliance store until 1999, changed ownership, the subsequent owner completing some renovations and retaining the old recording equipment, allowing for tours of the property.

[16] In 2013, the documentary Muscle Shoals raised public interest in a major restoration of the studio,[17] and in June that year, the owner sold the property (without the historic recording equipment) to the Muscle Shoals Music Foundation, an organization that had been formed earlier that year with the goal of establishing a music museum in the historic building.

[23] The building closed when major restoration work began in September 2015, and reopened as a finished tourist attraction operated by the Muscle Shoals Music Foundation on January 9, 2017.

The film includes interviews with Percy Sledge, Wilson Pickett, Aretha Franklin, Etta James, Mick Jagger, Keith Richards, Steve Winwood, Bono, Alicia Keys and many others.