Sixth-ranked Spaniard Muguruza reached her first USA event final by trouncing Czech top-ranked defending champion Karolina Pliskova 6-3, 6-2, flipping the script in a rematch of their 2016 Cincinnati semi-final.
"I managed, don't lose the courage, and I turned (it) around", Muguruza said. "I win against the 15th player in the world playing not like I want and I m really happy about it".
Muguruza advanced to Sunday's final against the victor of a later match between Romania's second-ranked Simona Halep and 151st-ranked United States wildcard Sloane Stephens.
Despite the loss, Nadal will move back to No. 1 in the ATP rankings next week for the first time since 2014, before a series of injuries affected his game. Pliskova requested her coach midway through the match but the Spaniard surged ahead 5-3, executed another break and nabbed the set.
Muguruza will play for her fifth career title Sunday against the victor of a later match between Romania´s second-ranked Simona Halep and 151st-ranked United States wildcard Sloane Stephens. She wasted another match point before Muguruza took it to the tiebreaker and dominated. I returned well. My shots were there.
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Last month, Muguruza won her second Grand Slam after the 2016 French Open and her fourth career title on the All-England grass.
Pliskova's two-in-one effort, matching feats on her way to Eastbourne and Doha titles, means Halep must capture the crown to swipe the top spot in Monday's rankings. She was runner-up to Serena Williams in 2015.
The Spaniard kept the pressure on Pliskova's serve, securing a key break to lead 4-2 in the second set before closing out victory in one hour and 21 minutes after taking a fifth match-point chance against the top seed. Pliskova had 28 unforced errors to Muguruza's 13.
"I had it on my mind", Muguruza said. I'll try everything tomorrow. "So I hope to keep it going".
No matter who wins Sunday's women's singles title at the Western & Southern Open, history will be made. She contacted relatives to make sure they were fine.
The results (third round): Men: Grigor Dimitrov bt Juan Martin del Potro 6-3, 7-5; Yuichi Sugita bt Karen Khachanov 6-7 (0), 6-3, 6-3; David Ferrer bt Pablo Carreno Busta 6-4, 6-4; Jared Donaldson bt Nikoloz Basilashvili 6-4, 7-6 (4); Dominic Thiem bt Adrian Mannarino 7-6 (4), 7-6 (3); John Isner bt Frances Tiafoe 7-6 (4), 7-5.