Benneteau managed what no other player at the tournament achieved -- breaking del Potro's serve twice in the first set -- but struggled to hold his own serve against the big-hitting Argentine and crumbled in the second set.
The 2009 U.S. Open winner was the runner-up in Rotterdam last year.
Benneteau, who beat No. 2-ranked Roger Federer in the quarterfinals, is winless in eight ATP finals.
"We are getting closer and closer. I am sure with you I can win a title," Benneteau said as he thanked his coach.
Benneteau saved four match points when serving at 5-2 in the second set, but del Potro then served out the match.
While Benneteau managed to break the 6-foot-6 Argentine, del Potro hit back immediately, breaking Benneteau as he reeled off four straight games to take command of the opening set.
Benneteau saved two set points on his own serve at 5-3 and then broke del Potro a second time on his way to forcing a tiebreaker. But the experienced del Potro dominated to take the set.
Benneteau seemed sluggish in the second set as del Potro ran away with the match, serving the final game with wadding in one nostril after suffering a nose bleed.