Conn debuted as a professional boxer on June 28, 1934, losing to Dick Woodard by a decision in four rounds. His first win came almost a month later, on July 20, against Johnny Lewis, by a knockout in three rounds.
Conn built a record of 47 wins, 9 losses and 1 draw (tie), with 7 knockout wins, before challenging for the world's Light-Heavyweight title. Along the way, he beat former or future world champions Fritzie Zivic, Solly Krieger and Fred Apostoli, as well as Teddy Yarosz and Young Corbett III.
On July 13, 1939, he met world Light-Heavyweight champion Melio Bettina in New York, outpointing him in 15 rounds and winning the world's Light-Heavyweight championship. Conn defended his title against Bettina, and twice against another world Light-Heavyweight champion, Gus Lesvenich, each of those three bouts resulting in 15 round decision wins for Conn. Conn also beat Bob Pastor, former world Middleweight champion Al McCoy, and Lee Savold in non-title bouts during his run as world Light-Heavyweight champion.
In May of 1941, Conn gave up his world Light-Heavyweight title to challenge world Heavyweight champion Joe Louis. Conn attempted to become the first world Light-Heavyweight champion in boxing history to go up in weight and win the world's Heavyweight championship when he and Louis met on June 18 of that year. The fight became part of boxing's lore because Conn held secured lead on the scorecards leading to round 13. According to many experts and fans who watched the fight, Conn was outmaneuvering Louis up to that point. In a move that Conn would later regret for the rest of his life, he tried to go for the knockout in round 13, and instead wound up losing the fight by knockout in that same round himself.
In 1942, Conn beat Tony Zale and had an exhibition with Louis. World War II was at one of its most important moments, however, and both Conn and Louis were called to serve on the Army. Conn went to war and was away from the boxing rings until 1946.
By then, the public was clamoring for a rematch between him and the still world Heavyweight champion Louis. This happened, and on June 19, 1946, Conn returned into the ring, straight into a world Heavyweight championship bout. The fight, at Yankee Stadium, was the first televised world Heavyweight championship bout ever, and 146,000 people watched it on TV, also setting a record for the most seen world Heavyweight bout in history. Most people who saw it agreed that both Conn and Louis' abilities had eroded with their time spent serving the United States, but Louis was able to retain the crown by a knockout in round eight. Conn's career was basically over after this fight, but he still fought two more fights, winning both by knockout in round nine. On December 10, 1948, he and Louis met inside a ring for the last time, this time for a public exhibition in Chicago. Conn would never climb into a ring as a fighter again.
Retiring from the ring as a boxer did not mean retiring as a public figure for Conn. As he became an older citizen, he participated in a number of documentaries for HBO, and he was frequently seen at boxing related activities until his death in 1993, at the age of 75.
He had a professional boxing record of 63 wins, 11 losses and 1 draw, with 14 wins by knockout.