As it happens, Thiem was the last player to take a set from Nadal on clay, beating the top-ranked player in the world at the Rome Open on May 19 of past year.
Nadal surpassed the achievement of John McEnroe, who in 1984 on the carpet managed to win 49 sets in a row.
"I won 50 straight sets on this surface", he said. In their match today, the third round of Madrid Open, Nadal lost the first set initially 7-5, despite saving a couple of set points before. Anderson, the 31-year-old US Open runner-up last year, hit 15 aces and 35 winners.
Thiem didn't back down after his first set win, pushing Nadal to the brink and eventually putting him away in straight sets.
The fifth-seeded Thiem arrived at the semifinals after dealing top-ranked Rafael Nadal his first loss on clay in a year. "I feel like every time we play, we have a thriller match".
"Of course I'm upset", Nadal admitted.
World number one Rafael Nadal will continue his quest for sixth Madrid Open title when he squares off with Argentinean tennis star Diego Schwartzman in the last-16 clash of the men's singles event here on Thursday.
World number 7 and defending Madrid finalist Dominic Thiem is through to his second Masters 1000 final after a commanding 6-4 6-2 win over the 6th seed Kevin Anderson in an hour and 25 minutes. "I tried to fight back, but I wasn't good enough and he was better".
While Thiem admits the conditions in Madrid suit him perfectly - it is where he reached his first Masters 1000 final previous year - he also believes he produced exceptional tennis to overcome the King of Clay.
The second set proved a no-contest as Zverev took complete control against a dispirited looking opponent.
Nadal has already won two ATP titles this year and could triumph in Madrid to secure a 78th ATP title. He was beaten again at 4-3 and finally at 6-3 to end his unbeaten run.
He'll face Denis Shapovalov in Friday's quarter-final, after the Canadian beat compatriot Milos Raonic 6-4, 6-4.
It was a brief reprieve as a lazy forehand volley gave Thiem a 6-5 advantage and the set came the Austrian's way in the 12th game off an ace. Earlier in the day, the tall South African defeated Dusan Lajovic 7-6 (3), 3-6, 6-3.
On the women's side, Kiki Bertens beat seventh-seeded Caroline Garcia 6-2, 6-2 to advance to the final.
He won 21 matches on clay and 50 sets.