World No 8 Anderson reached the last four after his 7-6 (7-3), 3-6, 6-3 victory over Serbian qualifier Dusan Lajofic in Friday's quarterfinals.
The set was soon wrapped up regardless, before Thiem quickly moved two breaks up in the second as his opponent failed to live with a dominant display. But the remarkable streak was brought to an end by Thiem, who refused to let the momentum slip after winning the first set 7-5.
Thiem, meanwhile, was aware of how significant the win was, especially considering his recent 6-0, 6-2 loss to Nadal at the Rolex Monte Carlo Masters.
Early in the second set, Nadal was in trouble again.
In the quarterfinal match, Lajovic held his service games and battled Anderson to a tiebreak in the first set.
But Nadal again lost his serve.
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By this stage, though, Thiem did not need anybody telling him that he was on his way to a major upset victory. These are three months or more given away.
King crusher: A crestfallen Nadal congratulates Thiem after the match.
In the Madrid semi-finals on Saturday, Thiem faces big-serving South African Kevin Anderson, who has beaten the Austrian in their last six encounters. He won the match 6-4,6-2 and will now be playing the victor of the match between Alexander Zverev and Denis Shapovalov.
After the match, Thiem said that his make-or-break approach to playing Nadal had paid off. "I think the level of my game increased especially in this week". "It has to be a special day - the shots have to work - and that was the case today". Coincidentally, it was Thiem who last beat Nadal on clay, at last year's Rome Masters, shortly before the Spaniard rampaged to a 10th French Open title without dropping a set. "I think it has just been a match where he was better than me, same as a few weeks ago I was better than him".
"I think that today I wasn't reading the ball well enough to be able to handle the situation, to put him in places where he didn't feel comfortable to play", explained a disappointed Nadal after the match. "It's hard to be able to win 50 sets in a row", Nadal said. "That's what I'm working on", Nadal said, as quoted by ATP's official website. Thiem made the finals past year. He did not play another match on tour until mid-April.
"Five months without playing in a tournament means that I can not be No 1".