His career began with "The Fat Man" (1949, Imperial Records), one of the first rock and roll records, featuring a rolling piano and Fats doing wah-wah vocalizing. The record, a reworking of "Junker's Blues" by Champion Jack Dupree, was a massive hit, selling over a million copies and peaking at #2 on the Billboard R&B Charts. He also scored a hit with his funky version of the corny ballad "Blueberry Hill".
Fats then released a series of hit songs with producer and co-writer Dave Bartholomew, saxophonist Alvin "Red" Tyler and drummer Earl Palmer. Fats finally crossed into the pop mainstream with "Ain't That a Shame" (1955) which hit the Top Ten, though Pat Boone characteristically hit #1 with a cover of the song. Fats released an unprecedented series of 35 Top 40 singles, including "Whole Lotta Loving" and "Blue Monday".
After moving to ABC-Paramount in 1963, the bottom fell out of Fats' recording career although he continued as a popular live act. Though he remained active for decades, he only had one more Top 40 hit, a cover of the Beatles song "Lady Madonna", originally written by Paul McCartney to emulate Fats's style.
In the 1980s Domino decided he would no longer leave New Orleans, as he had a comfortable income from royalties, disliked touring, and claimed he couldn't get any food he liked anywhere but his home town. His induction into the Rock and Roll Hall of Fame and an invitation to perform at the White House failed to get Domino to make any exception to this policy. He lives in a mansion in the mostly working-class 9th Ward neighborhood, where he is a familiar sight in his bright pink Cadillac. He makes yearly appearances at the New Orleans Jazz and Heritage Festival and a few other local events, where he demonstrates that his musicianship and showmanship are undiminished.