Denning made his big-league debut on April 15, 1942 against the Detroit Tigers, and lashed two hits in four at bats, including a double, off Dizzy Trout in a 6–2 Cleveland defeat.[1] He started at catcher again the following day, and went one for two, with another double (off Tommy Bridges).[2] But, although he was the Indians' most-used catcher (playing ahead of rookie and eventual Cleveland stalwart Jim Hegan and veteran Gene Desautels), Denning's production declined as the season wore on. He batted only .210 in 92 games, and, in 1943 he served as the Indians' reserve first baseman (backing up Mickey Rocco) through June 4, when he returned to the minor leagues for the remainder of his on-field career.
In the Majors, Denning collected 76 hits, with 20 doubles and one home run, struck on May 4, 1942, at Fenway Park off Dick Newsome of the Boston Red Sox. He became a player-manager in the minors in 1948 in the Chicago White Sox organization, retiring as an active player in 1950 before spending a final season, 1951, as a non-playing skipper.