Del Potro, 2009 U.S. Open champion, briefly wobbled while down 0-30 and serving for the match, but the fourth-seeded Argentine closed it out when Llodra netted a forehand.
"This is something special for me. I'm very glad to win this tournament in my first (appearance)," he said. "I'm sorry I beat three French players in this tournament. I feel really happy to win here. I hope I can play again next year."
Llodra, who won in Marseille in 2010, lost his serve once in each set and could not force a single break point chance against del Potro, who hit 11 aces to 10 for the Frenchman.
"He played really, really well today and I had no virtually no chances, except in the last game when he was 0-30 down," Llodra said. "It was a great game from him, and for my part I was a bit more tired than in recent days."
Del Potro lost to Roger Federer in his last two tournaments, including in the ABN Amro final last Sunday in Rotterdam, Netherlands -- where he also beat Llodra in the first round.
The 23-year-old del Potro raised his hands in the air, closed his eyes and then pumped his fists after beating Llodra.
"I'm getting older but I sometimes play more smart than three or four years ago," del Potro said. "Today was a really tough match, you need to play 100 percent. It's very tough when he serves and he plays good volleys, drop shots. Finally I closed the match with my serve and now I can breathe again."
Llodra looked strong on serve in a fast-paced opening set, but del Potro took a decisive advantage when he broke in the ninth game and held serve easily to win the first set.
Del Potro broke Llodra in the fifth game of the second set and held for a 4-2 lead, meaning the 31-year-old Llodra had too much to do as he tried to vary his game.
Showing rare signs of pressure when serving for the match, del Potro quickly fell behind 0-30 -- and faced pressure on his second serve on the next point -- to briefly raise hopes of the French fans at the Palais des Sports.
But a strong second serve pinned Llodra behind the baseline and del Potro whipped a backhand inside the line to get back to 15-30. He then served an ace for 30-30.
Llodra charged forward on the next point. His forehand sailed wide to give del Potro his first match point. After a brief rally, Llodra made an awkward return close to shoulder height and returned it weakly into the net.
"It's been a good week for me, although it's always frustrating to miss out," said Llodra, who has five career singles titles and 23 in doubles. "I'm a bit disappointed, but that's the way it goes."