Piola began his career with Italian club side Pro Vercelli, making his Serie A debut against Bologna on 16 February 1930, scoring 13 goals in his first year, at the age of 17.

Piola went on to play 34 games for Italy and score 30 goals between 1935 and 1952, a tally that would surely have been greater if not for the interruption caused by World War II.

[19] Regarded as one of the greatest strikers of all time, Piola was widely renowned for his goalscoring ability throughout his career, and his eye for goal.

[20] He was considered to be a modern and well-rounded player during his time, as he used his physical attributes, intelligence, and control to play with his back to goal, and lay off the ball for teammates in order to provide them with assists.

[21][20] Piola particularly excelled as a centre-forward, however; his speed, positional sense, offensive movement, and opportunism enabled him to lose his markers with his attacking runs and receive his team-mates' deliveries or pounce on loose balls in the area.

Piola was also known for his powerful and accurate finishing ability with his head and both feet, from any position on the pitch, which made him a prolific goalscorer throughout his career.

[21][20][23][24] Due to his agility and athletic ability, Piola also excelled in the air, and he was capable of scoring spectacular acrobatic goals from volleys and bicycle kicks.

Unlike his legendary international team-mate, club rival, and friend Giuseppe Meazza,[25] however, with whom he was often compared,[26] Piola was much more reserved both on and off the pitch, and he preferred to score through efficiency and pragmatism rather than flamboyance.