Spence was transferred from Scotswood to in March 1919  Manchester United  sold. He made his debut on August 30, 1919 against  Derby County . Spence stayed with the Red Devils until 1933, playing a total of 510 games and scoring 168 goals. He was one of the only Red Devils players in the interwar period to be considered a "star". Spence served in the  First World War  for the British Army and during the war he was a guest player with  Liverpool FC  and Newburn. Spence didn't win a single title and is still among the ten players who made the most competitive games for ManUtd.