Holmes won his first 48 professional bouts, including victories over Norton, Ali, Earnie Shavers, Mike Weaver, Gerry Cooney, Tim Witherspoon, Carl Williams and Marvis Frazier, and falling one short of matching Rocky Marciano's career record of 49–0 when he lost to Michael Spinks in 1985. Holmes retired after losing a rematch to Spinks the following year, but made repeated comebacks. He was unsuccessful in three further attempts (against Mike Tyson, Evander Holyfield and Oliver McCall) to regain the heavyweight title, the last in 1995. Holmes fought for the final time in 2002, against Eric "Butterbean" Esch, and ended his career with a record of 69 wins and 6 losses. He is frequently ranked as one of the greatest heavyweights of all time and has been inducted into both the International Boxing Hall of Fame and World Boxing Hall of Fame.

This red Everlast boxing glove was signed in black by Holmes and includes a Schwartz Sports hologram and COA.