Born in Altoona, Pennsylvania, he grew up in nearby Nanty Glo, where he was a standout in sandlot baseball in his youth. Collins started his professional baseball career in 1923. He played in various minor leagues for eight seasons until 1930, when he hit .376 with 40 home runs for the Rochester Red Wings of the International League. His 180 runs batted in set an IL record.
For that performance, Collins was called up to the majors. As a member of the Gashouse Gang Cardinals teams, Collins had a breakout season in 1934 with 35 home runs (a league-leading total), 128 runs batted in, and a .333 batting average. He also hit .367 in the World Series, which the Cardinals won in seven games.
Collins is the only first baseman to have twice recorded no putouts in a nine-inning game - once for the Cardinals in 1935, and again for the Cubs in 1937. Between his time with the Cubs and the Pirates, Collins spent two years with the Los Angeles Angels, and played in 346 games during that time.
Collins played in the Pacific Coast League and Eastern League after his major league career was over. In 1944, he was named Minor League Player of the Year while with Albany of the Eastern League. That season – at the age of 40 – he managed to hit .396 with a league-leading 40 doubles.