But the 22-year-old French Open champion downplayed her chances following a 2-6 6-0 6-3 win over Belgian qualifier Elise Mertens in the opening round on Monday, telling the courtside crowd it would take a miracle for her to reach the final.
While it might not require divine intervention, Muguruza's record at the year's final grand slam indicates she will need to produce something special, having never ventured beyond the second round in three previous visits to Flushing Meadows.
"I think is different. Someone that has reached the last rounds of the tournaments you believe, maybe I can do it again," Muguruza said. "You have more expectations, that's for sure.
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"For sure, maybe a lot of people are talking. All this kind of stuff that I cannot control ... if I cannot control it, I don't put it in my bag."
Beyond her resume and ranking, Muguruza's opening match offered little hint that a second grand slam is there for her taking.
The Spaniard needed almost two sloppy hours to dispose of Mertens, committing seven double faults while converting just six of 15 break chances while the 137th-ranked Belgian made the most of her opportunities, breaking Muguruza four of five times.
Muguruza stunned the tennis world by overpowering Williams to win the French Open title in June and could take over the world number one spot from the American this fortnight.
A self-described country girl, Muguruza is not a big fan of the bright lights of New York but the Spaniard had better prepare herself for the Big Apple spotlight, which will get brighter with each victory she achieves.
"For me, it's difficult during the tournament," said Muguruza, who will next meet 48th-ranked Latvian Anastasija Sevastova. "I came one week earlier here to prepare and everything.
"I felt there's more movement, more noise, more stuff. It's well known also because of the environment and the crowd and the vibes, that feeling that brings New York.
"I think it's also special. There's a lot of people. They're watching you. Maybe it's not as silent as Wimbledon, that everybody is like this, but I enjoy."
(Editing by Mark Lamport-Stokes)
