Nejedlý played for Sparta Prague in his entire career. He scored 162 league goals in 187 games, winning four Czechoslovak First League championships in 1932, 1936, 1938 and 1939, adding a Mitropa Cup in 1935. He also scored 18 goals in 38 games for SK Rakovník (1943, 1944 and 1946), giving him a total of 180 league goals in 225 games.
For Czechoslovakia, Nejedlý scored 29 goals in 44 games. He was awarded the Bronze Ball in the 1934 World Cup as the third most outstanding player of the tournament and was voted into the All Star Team of the tournament. He was also top goalscorer. He would have gone on to play more games and score more goals for the Czechoslovakia had he not broken his leg in the 1938 World Cup which effectively ended his International career.
He was a participant in two World Cups, in 1934 in Italy and 1938 in France. Nejedlý was the outright top scorer in the 1934 World Cup with five goals. This has been officially recognized by FIFA since November 2006, as he was initially credited with only four, making him joint top scorer with Angelo Schiavio and Edmund Conen. He also scored two goals in 1938.