Second seed Nadal outfought Argentine Juan Ignacio Chela 7-5 7-5 and third seed Roddick overcame Croatian Ivan Ljubicic 7-6 7-6.
In a tight contest in which both players launched huge strokes from the baseline, twice French Open champion Nadal was more secure on the big points than his opponent.
The Spanish world number two forced Chela into a backhand error to break him to 6-5 in the second set and won the match when the south American made another mistake on his backhand.
"Chela is difficult player because he change a lot of the rhythm of the game," Nadal told reporters. "He sometimes plays slow, fast, sometimes with top speed, and then flat.
"That's difficult. The important thing is I wasn't playing my best match today, but I won."
Since winning his second French Open crown last June, Nadal has only reached one final, at Wimbledon, where he lost to world number one Roger Federer.
This will be only his second appearance in a semi-final this year but with Federer out of the tournament he should be confident of winning the title.
"I feel so much better than the last months right now," Nadal said. "I'm in a good way, because I'm playing my best level. So that's the goal, just play good and find the best feeling."
Roddick has yet to face break point in four matches in the tournament, and Ljubicic could not penetrate his service as Roddick fired 12 aces and a slew of service winners and backed them up with huge forehands.
Ljubicic fought off one set point at 6-5 with a backhand volley winner but Roddick cashed in on his second with a backhand crosscourt to clinch the tiebreak 9-7
Roddick needed four match points in a brilliantly played second set tiebreak which he won 10-8, finally closing out the match with a hard return at Ljubicic's feet.
"I had a couple of pretty good looks at match points, and especially that volley," Roddick said. "I was excited because I was playing the way I wanted to in the breakers. I gave myself a chance to win and eventually was able to do it."
Nadal and Roddick have not met since the Davis Cup final in 2004 in Seville, a match the Spaniard dominated a few months after the American had crushed him at the U.S. Open.
"I understand that he passes well and that he moves real well, but I have to move forward and have to play aggressive against him," Roddick said.
British No. 1 Andy Murray plays his quarter-final on Friday against ninth seed Tommy Haas. Serb Novak Djokovic plays Spain's David Ferrer in the other quarter-final.
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