Rafael Nadal defeated Stefanos Tsitsipas in the final, 6–4, 6–7(6–8), 7–5 to win the singles title at the 2021 Barcelona Open.

Nadal saved a championship point en route to his record-extending 12th Barcelona Open title and 61st ATP Tour singles title on clay.

It became the second tournament at which Nadal had earned 12 or more victories, after the French Open.

Tsitsipas, who had also lost to Nadal in his first career ATP singles final at this tournament in 2018, was in contention to win his first ATP 500 tournament title on his seventh attempt.

[1] Dominic Thiem was the reigning champion from when the tournament was last held in 2019,[2] but he did not return to compete.