Mugabi was part of an exceptionally talented group of light-middleweights and middleweights during a "golden era" of the 1980s which included Marvin Hagler, Sugar Ray Leonard, Thomas Hearns, Wilfred Benítez, and Roberto Durán.

As an amateur, Mugabi won a silver medal in the welterweight division at the 1980 Summer Olympics, and was the only medallist for Uganda at the event.

John Mugabi started as a professional on December 5, 1980, by knocking out Oemer Karadenis in round one in Cologne.

Searching for more formidable foes, John moved to Florida where he became a favourite of American TV networks with his sensational knockouts of contenders such as Curtis Ramsey, Gary Guiden, former world champion Eddie Gazo, Curtis Parker, Frank The Animal Fletcher, Nino Gonzalez and Earl Hargrove through a display of tenacity and ferociousness.

Nicaraguan, Eddie Gazo, a former WBA Junior Middleweight Champion provided Mugabi with his first real test.

On his way to becoming the number one contender for the middleweight title of each of the three major sanctioning bodies (WBA, WBC, and IBF),[2] Mugabi ran roughshod over the division and finished each of his opponents inside the distance.

Writing in the New York Times in 1986, Berger, commenting on Mugabi’s preparation for the Hagler fight noted the intensity of preparation that left his sparring partners in a 'woebegone condition' and further that some did not last long enough to draw their second paycheck and left Mugabi’s training camp ‘looking like extras from 'Night of the Living Dead'.

Mugabi fought back gamely but his early knockout wins left him ill-prepared for a long, tough fight.

Mugabi went down in weight and was given an opportunity by the WBC to win their world light middleweight title, vacated by Hearns.

In January 1988, he came back to fight Bryan Grant on the undercard of Mike Tyson's title defence against Larry Holmes.

He became number one contender for the WBC 154 lb title in August 1988 but could not land a fight with then-champion Donald Curry.

On July 8 of that year, Mugabi finally made his dream come true, when Curry's successor Rene Jacquot could not continue the fight due to an injury in round one in Grenoble to become the WBC light middleweight champion.

After two first-round knockout wins against Ricky Stackhouse and Carlos Antunes, Mugabi, who by this time was having difficulty making the weight limit of 154 lbs, put his title on the line against Terry Norris.

Showing resilience, Mugabi resurfaced with two more wins and once again found himself fighting for a world title, facing Gerald McClellan on November 20, 1991, in London for the vacant WBO middleweight championship.

That November night in 1999, marked the decline of Mugabi’s illustrious boxing career as he was again knocked out in the eighth round.