Nadal finished off a 7-5, 3-6, 6-3 victory over his American opponent with a 128-mph ace, then sank to his knees and thrust his arms skyward
He had finally taken the upper hand in the tight match when he broke Blake's service for a 5-3 lead in the third set.
The Spaniard, ranked No. 2 behind Roger Federer, then served out without losing another point.
The ninth-ranked Blake had beaten Nadal in the U.S. Open in 2005, then defeated him twice in 2006, including the semifinals in Indian Wells
Nadal said that ending Blake's streak against him wasn't the big thing, but "the thing is being in the semifinals and beating two big players like (Jo-Wilfried) Tsonga and Blake. It was two very important matches."
He added, "Right now, I have had a very good tournament."
The 28-year-old Blake complimented Nadal, still just 21 despite his long list of tour accomplishments.
"He's No. 2 in the world for a reason, and he did make his presence felt out there," Blake said. "I didn't do enough to hurt him on the big points."
Nadal will face Australian Open champion Novak Djokovic in Saturday's semifinal. Federer, on the other side of the bracket, will play Tommy Haas in one quarterfinals match Friday, with Mardy Fish going against David Nalbandian in the other.
Two-time champion Lindsay Davenport went out of the tournament earlier in the day, having to quit after one set because of a sore back. Jelena Jankovic won the set 6-2.
Davenport, who has had back trouble in the past, said she thought lingering tightness might go away while she was playing.
"It was pretty obvious to me after two games that I was pretty sore, and it was hard to rotate," she said. "I tried to do the best I could. But sometimes these things happen, and when you're familiar with an injury, you kind of know right away what you're up against."
Davenport hopes the problem will clear up quickly so she can play at Miami in the tournament that begins next week.
"We'll just have to see what the next few days bring," she said.
Djokovic and Ana Ivanovic, both 20-year-old Serbs who have joined the ranks of tennis' elite, won matches in straight sets to gain the semifinals.
Djokovic defeated Stanislas Wawrinka 7-6(5), 6-2, and No. 2 Ivanovic beat Vera Zvonareva 6-1, 6-4.
No. 3 Djokovic, down 6-5 in the opening set, broke Wawrinka's serve to set up the tiebreaker. Then, when Wawrinka was unable to return his volley for the final point of the tiebreaker, Djokovic celebrated by dropping to his knees, yelling in glee and pounding his chest with both hands.
"I'm a very emotional player on the court and very emotional person off the court as well," said Djokovic, also known for his wry sense of humor. "As you could see by the reaction, it was one of the -- not one of the, probably the most important point of the match."
It proved a turning point, as he went on to take clear control in the second set.
Ivanovic, who lost to Maria Sharapova in the Australian Open final, will face Jankovic in one all-Serbian semifinal on Friday, with the other pitting Russians Sharapova and Svetlana Kuznetsova.
The women's and men's finals are on Sunday.