During World War II, many regular players from the Reds and other Major League teams were unavailable while serving in the military. Meanwhile, Nuxhall was the biggest member of the ninth grade class in nearby Hamilton, Ohio at 6′ 2″ and 190 pounds - a left-hander with a hard fastball, but not much control. He had already been playing in a semipro league with his father for a couple of years. Scouts looking to fill out the Reds' depleted roster were told his father wasn't interested in signing a professional contract because of his five children, so they asked about the son, who was only 14 at the time. After waiting until basketball season was over the next year, Nuxhall signed a Major League contract with the Reds on February 18, 1944. General Manager Warren Giles intended to wait until school was over in June to add him to the team, but more players were inducted into the service in the spring, and Nuxhall was in uniform with the team on Opening Day with permission from his high school principal.

On June 10, the Reds were playing the first place St. Louis Cardinals at Crosley Field and trailing 13-0 in the ninth inning when Manager Bill McKechnie called on Nuxhall to enter the game. He started well by retiring two of the first three batters he faced, but ended up allowing five walks, two hits, two wild pitches and five runs before being relieved. He spent the rest of the 1944 season in the minor leagues, but unlike Jake Eisenhart, who also made his debut for the Reds on June 10 and got the last out, Nuxhall would return to pitch in the Majors again.

Following his appearance with the Reds, he was assigned to the Birmingham Barons in the Southern League, but pitched only a third of an inning there (he struck out his first batter, then allowed a hit, five walks, a hit batter and five runs). Nuxhall attended Spring training with the Reds in 1945, but decided to remain home until he finished high school the following year. He regained his amateur status and played football, basketball and baseball for Hamilton High School as a senior in 1946, earning all-state honors in football and basketball. Over the next five years, Nuxhall played in the minor leagues with Syracuse, Lima, Muncie, Columbia, Charleston, and Tulsa before returning to the Reds in 1952.

Nuxhall spent almost 15 of his 16 Major League seasons with Cincinnati, where he was a two-time National League All-Star and led the league in shutouts in 1955. He also played for the Kansas City Athletics and Los Angeles Angels in the American League. Second Career