Grimes was born in Newport News, Virginia, United States,[1] and began his musical career playing drums and one-fingered piano.

[2] After leaving Tatum, Grimes recorded with his own groups in New York and with a long list of leading musicians, including vocalist Billie Holiday.

He made four recordings with his own group, augmented with Charlie Parker: "Tiny's Tempo", "Red Cross", "Romance Without Finance", and "I'll Always Love You Just the Same", the latter two featuring Grimes' singing.

In the late 1940s, he had a hit on a jazzed-up version of "Loch Lomond", with the band billed as Tiny "Mac" Grimes and the Rocking Highlanders[1] and appearing in kilts.

[3] With Paul Williams, he co-headlined the first Moondog Coronation Ball, promoted by Alan Freed in Cleveland, Ohio, on March 21, 1952, often claimed as the first rock and roll concert.