The fifth-seeded Del Potro beat Ferrer 6-1, 7-5 to end the defending champion's chance to repeat at the ATP event.
"It was a very tough match against one of the best players in the world,'' Del Potro said. "He won here last year and has been playing well.''
Del Potro will play Richard Gasquet in the semifinals. The fourth-seeded Frenchman defeated Germany's Rainer Schuettler 6-3, 6-2.
Second-seeded Roddick cruised to a 6-3, 6-4 victory over Viktor Troicki for another semifinal berth. Roddick will face Tomas Berdych, who beat third-seeded Fernando Gonzalez, 6-0, 6-4.
After cruising through the first set, Del Potro broke Ferrer in the eighth game of the second set to take a 5-3 lead. Ferrer got back on serve, but Del Potro broke in the final game, hitting a crosscourt forehand winner on match point.
"I tried a lot things,'' Ferrer said. "But Juan Martin is very confident. He's been winning a lot of matches lately and played very well today.''
Ferrer had won his two previous meetings with the 20-year-old Del Potro, who has won 28 of his last 29 matches.
Roddick, coming off winning the China Open on Sunday, was in control from the outset against Troicki, who advanced to the quarterfinals on Thursday when his opponent, Jo-Wilfried Tsonga, retired from his third-round match with an abdominal strain.
"That's the best I've played so far,'' said Roddick. "I didn't serve as well as I have the last couple of days but I played better from the baseline. Hopefully, I can put the two together on the weekend.''
Roddick, coming off winning the China Open on Sunday, was in control from the outset against Troicki, who advanced to the quarterfinals on Thursday when his opponent, Jo-Wilfried Tsonga, retired from his third-round match with an abdominal strain.
"That's the best I've played so far,'' Roddick said. "I didn't serve as well as I have the last couple of days but I played better from the baseline. Hopefully, I can put the two together on the weekend.''
In the WTA event, top-seeded Caroline Wozniacki coasted to a 6-4, 6-1 victory over seventh-seeded Tamarine Tanasugarn to reach the semifinals.
Wozniacki will face Jarmila Gajdosova, who is in the draw as a lucky loser. Gajdosova beat Klara Zakopalova 7-5, 7-5.
The other semifinal will be between No. 5 Kaia Kanepi, who beat Anastasia Pavlyuchenkova 7-6 (4), 7-6 (1), and No. 8 Aleksandra Wozniak, who downed Samantha Stosur 7-5, 6-3.
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