Williams will face Canadian Bianca Andreescu for the US Open title as the American sets herself up for another attempt to clinch a record-equaling 24th Grand Slam singles title.
Ashleigh Barty ended Australia's 46-year wait for a French Open singles title by thrashing nervous Czech teenager Marketa Vondrousova in a one-sided women's final.
Tsitsipas had never won a set in his previous three meetings against claycourt specialist and 11-times French Open champion Nadal, but the Greek drew first blood by saving a break point to hold in the 10th game and take the first set.
Rafael Nadal showed no signs of rust as he raced into a 5-0 lead against fellow Spaniard Roberto Bautista Agut in the first set on Court Rainier III, defending his Monte Carlo Masters title with 6-1, 6-1.
US Open winner Sloane Stephens and world number one Simona Halep cruised into the final to set up a rematch of the French Open final.
Nadal earns a record-extending 11th championship at Roland Garros. The victory allows the 32-year-old Spaniard to hold onto the No. 1 ranking.
Simona Halep fought back from a set and a break down to finally achieve her "dream" of winning a Grand Slam title, beating Sloane Stephens 3-6, 6-4, 6-1 in a gruelling French Open final on Saturday.
Rafael Nadal is now just the second man to reach 11 finals at the same Slam, equalling Roger Federer’s mark at Wimbledon.
Top seed Simona Halep faces Spain's Garbine Muguruza in the semifinals as the Romanian bids to claim her maiden Grand Slam title.
12-time major champion Novak Djokovic of Serbia lost in the French Open quarterfinal to lowly-ranked Marco Cecchinato of Italy who rose to the occasion and will now face Dominic Thiem of Austria on Friday.
This was Williams' first major tournament in 16 months, and her first as a mother. Her baby was born last September.
The 21-year-old German looked to be on the brink of another disappointing early exit from a Grand Slam, but he held his nerve to force a tiebreak, which he won comfortably and . eventually prevailed.
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