He began performing at the age of eight, and booked his first night club at the age of thirteen.
His career took off after he moved to New York City in 1938. Early collaborations included Tab Smith, Billy Hick's Sizzling Six, the Roy Eldridge Orchestra, and six years with Lucky Millinder's Orchestra at Harlem's Savoy Ballroom.
Panama Francis spent five years recording and touring with Cab Calloway.
He also played with Duke Ellington, Tommy Dorsey, Ray Conniff, and Sy Oliver, becoming a highly successful studio drummer.
He recorded with John Lee Hooker, Eubie Blake, Ella Fitzgerald, Illinois Jacquet, Ray Charles, Mahalia Jackson and Big Joe Turner.
As Rhythm and Blues and Rock and Roll went mainstream Francis became even more sought after. He drummed on the Elvis Presley demos, and he is featured on hits by the Four Seasons ("Big Girls Don't Cry" and "Walk Like a Man"), the Platters ("Only You", "The Great Pretender", "Smoke Gets in Your Eyes" and "My Prayer"), Bobby Darin ("Splish Splash"), Neil Sedaka ("Calendar Girl"), and Dion ("The Wanderer").
He drummed on "Prisoner of Love" for James Brown, "What a Diff'rence a Day Makes" for Dinah Washington, "Drown in My Own Tears" for Ray Charles, "Patricia" for Perez Prado and "Jim Dandy" for LaVern Baker.
In 1979, Panama Francis reestablished the Savoy Sultans touring, recording several Grammy-nominated albums, and keeping residence at New York's prestigious Rainbow Room through the mid-1980s.
He appeared in several films with Cab Calloway: Angel Heart, Lady Sings the Blues, The Learning Tree.
Panama Francis received a Pioneer Award from the Rhythm and Blues Foundation in 1993 and was also inducted into the Smithsonian National Museum of American History.
His drum sticks are on display at the Rock and Roll Hall of Fame.