Robert Cray was among artists such as Stevie Ray Vaughan and George Thorogood, who got wider radio airplay and regular MTV video exposure during the late 1980s. He started playing guitar in his early teens. At Denbigh High School in Newport News, Virginia, his love of blues and soul music flourished as he started collecting records. Originally, Robert Cray wanted to become an architect, but at about the same time he was going to study design in architecture he formed a local band "Steakface", described as "the best band from Lakewood you never heard of". Cray on guitar and vocals contributed greatly to Steakface's set list of songs by Hendrix, Quicksilver Messenger Service, Fleetwood Mac, the Grease Band, Blodwyn Pig, Jethro Tull, Forever More, Spirit, and the Faces. By the time he was twenty, Cray had seen his heroes Albert Collins, Freddie King and Muddy Waters in concert, and decided to form his own band. His band started playing college towns on the west coast. After several years of regional success, Cray was signed to Mercury Records in 1982. His third release, Strong Persuader, received a Grammy Award, while the crossover single "Smokin' Gun" gave him wider appeal and name recognition.

By now, Cray was an opening act for major stars, such as Eric Clapton (who remains a loyal friend to this day), and sold out larger venues as a solo artist. By the early 1990s his name was immediately associated with his soothing, soulful voice, crisp, clean guitar work, and innovative modern blues sound. Cray has generally played Fender guitars (Telecasters and Stratocasters) and there are two signature model Robert Cray Stratocasters available from Fender. The Robert Cray Custom Shop Stratocaster is made in the U.S. in the Fender Custom Shop and is identical to the guitars that Cray currently plays, while the Robert Cray Standard Stratocaster is a less-expensive version made in Fender's Ensenada, Mexico plant.

Cray also had the opportunity to play alongside John Lee Hooker, on his album Boom Boom. Cray plays the guitar solo in the song "Same Old Blues Again". He also features on the critically acclaimed album, The Healer, another recording from John Lee Hooker. Cray plays a guitar solo on the song "Baby Lee".

He continues to record and tour. Cray appeared multiple times on Eric Clapton's Crossroads Guitar Festival, and is currently supporting 'Slowhand' on his 2006-2007 world tour.

Also, in the film Animal House, Cray plays the unaccredited bassist in Otis Day and the Knights.