The top-seeded Federer jumped to a 5-0 lead in the first set, with del Potro making uncharacteristic errors. Del Potro, who beat Federer in the 2009 U.S. Open final, took a 2-1 lead in the second set before Federer won five of the next seven games to close the match.
"For me, it all began in 1999 when I reached the quarterfinals here," Federer said. "Even now, the expectations were high throughout the tournament. I am happy I was able to fulfill the expectations."
The Swiss star was making his first appearance in Rotterdam since winning the 2005 title. Del Potro, seeded third, was playing in the tournament for the first time.
Del Potro won just seven points on his serve in the first set. While the Argentine's game improved in the second, he couldn't find a way to beat Federer on the key points.
Federer, who beat Nikolay Davydenko in the semifinals, took a 4-2 lead before serving out the match to win his 71st career title. He saved all seven break points he faced and broke del Potro three times.
"I have managed to restore my rhythm," Federer said. "The match against Davydenko was a good warmup for the match against del Potro."