Nadal improved to a career-best 17-1 on the year, including 14 straight match wins. He's won three titles — two on clay while runner-up in another on his favorite surface — since returning from a left knee injury.
Maria Sharapova defeated Caroline Wozniacki 6-2, 6-2 to win her first title of the year in the women's final between two former top-ranked players.
Indian Wells is his first hard-court title since Tokyo in October 2010, having lost in six previous finals on the surface. He won his 600th career match and will move to No. 4 in the rankings released Monday.
Nadal broke a tie with Roger Federer with his record 22nd career ATP Tour Masters 1000 title. He earned $1 million for his third Indian Wells title.
Del Potro came up short in his bid to beat three Top-10 players in the same tournament for the second time in his career. He defeated No. 3 Andy Murray and No. 1 Novak Djokovic in three sets apiece in becoming the second Argentine since Guillermo Villas in 1977 to reach the final here.
Nadal served three love games in the third set, capping his last one with a 123-mph ace that gave him a 5-3 lead.
Del Potro came from love-40 down and fought off three match points to hold at 5-4. But Nadal served out the match, dropping just one point in the final game. As Del Potro's forehand sailed wide on his fourth match point, Nadal collapsed flat on his back after playing 2½ hours in the desert heat.
He got up and hugged Del Potro, then trotted behind the baseline to clasp hands with billionaire tournament owner Larry Ellison of Oracle Corp. before falling to his knees near the net and raising his arms in celebration. Nadal playfully took a bite out of the Baccarat crystal trophy.
Del Potro saved three break points to lead 1-0 in the third. Nadal held at love, taking three games in a row for a 3-1 lead that he never gave up.
Nadal blew a 3-0 lead in the first set. From there, Del Potro won eight of the next nine games to claim the opening set and a take a 2-0 lead in the second. He went up 3-1 before Nadal grabbed the momentum, winning the final five games and the set 6-3 on a 105-mph ace that capped a love service game.
Sharapova dictated from the opening game, when she broke Wozniacki at love with groundstrokes that had the Dane running from side to side. Sharapova faced just two break points on her serve in the nearly 1½-hour match.
"I always felt like I was always a foot ahead, especially with the breaks," she said. "I was able to serve well today, and that helped me."
It was Sharapova's second career title at Indian Wells, where she first won in 2006. Wozniacki won here in 2011. The women met in a final for the first time; their six other matches came in earlier rounds.
The Russian is projected to move one spot in the WTA Tour rankings to No. 2 on Monday, dropping Victoria Azarenka to third. Wozniacki will move up one spot to No. 9.
The victory, worth $1 million, gave Sharapova at least one title for 11 straight years dating to 2003.
Sharapova led 2-1 when Wozniacki brought her coach-dad Piotr out during a break. But she couldn't get untracked, and was broken again in the seventh game. Sharapova fought off two break points to take the first set in 38 minutes.
"She was putting pressure on me from the start. She was serving very well," Wozniacki said. "I felt like everything that she wanted to do today was going in. She was making very few errors, and if she did, then it was really at the times where it didn't really matter."
Sharapova broke to open the second set when Wozniacki double-faulted the game away. She converted her fourth break point on Wozniacki's backhand error to take a 5-3 lead. Sharapova was aggressive in her approach, using her forehand to push Wozniacki around and then coming in on short balls to easily put them away.
"I thought I was being aggressive, but I was doing the right things and being patient enough and looking for the right shot when I wanted to move in a little bit," Sharapova said.
"She's someone that if she has time she can make you hit so many balls, and that's not really the way that I want to be. It was really important to try to take away that time that she likes to have."
Sharapova went for it on her serves, too, winning 19 of 22 points on her first serve. Even when she sometimes missed going down the T, she kept changing up her placement.
Wozniacki struggled with Sharapova's serve, winning just 3 of 22 points on the Russian's first serve.
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