Mexico's Renata Zarazua pulled off a stunning upset by beating sixth seed Madison Keys while American Frances Tiafoe launched his latest bid to end the American men's drought at the US Open with a confident win over Japan's Yoshihito Nishioka.
Keys finally claimed her maiden major at the Australian Open this year but produced 89 unforced errors in the first match of the day on Arthur Ashe Stadium as she became the highest seed in the tournament to fall in a 6-7(10), 7-6(3), 7-5 defeat.
Zarazua, the only Mexican player in the US Open main draw, saved seven break points across the match for her first win over a top-10 player in a gruelling, three-hour and 10-minute affair.
"Coming into the match I was like almost crying because I was really nervous but I think the crowd made it so chill for me," she said. "I could hear some Mexican (fans) cheering so that was very nice."
She will hope to recreate the magic in the second round, where she faces Frenchwoman Diane Parry, who had no problems eliminating the twice Wimbledon winner Petra Kvitova 6-1, 6-0 in her final professional match.
The 17th seed Tiafoe provided the home fans some relief as he sent over 51 winners to beat Nishioka 6-3, 7-6(6), 6-3, closing out the afternoon programme on Ashe with his 19th ace.
The twice semi-finalist joins fourth seed Taylor Fritz and sixth seed Ben Shelton in the second round, as they aim to become the first American man to lift the US Open trophy in 22 years. He plays US qualifier Martin Damm next.
Twice major winner Barbora Krejcikova knocked out Victoria Mboko 6-3, 6-2 in the first match on Louis Armstrong Stadium after missing several months injured this year, weeks after the promising Canadian teenager's career breakthrough in Montreal.
She next plays Japan's Moyuka Uchijima.
Last year's semi-finalist Jack Draper dismissed Argentine qualifier Federico Agustin Gomez 6-4, 7-5, 6-7(7), 6-2 in the second match on Armstrong and plays Belgian Zizou Bergs next.
The British fifth seed is joined in the second round by compatriot Cameron Norrie, who advanced after American Sebastian Korda retired when trailing 7-5, 6-4. He will next play Argentinian Francisco Comesana.
The 19-year-old Brazilian fan favourite Joao Fonseca brought thrills to the Grandstand crowd as he kept his dream 2025 season on track with a 7-6(3), 7-6(5), 6-3 win over Serbia's Miomir Kecmanovic, setting up a meeting with 21st seed Tomas Machac.
US tennis royalty opens up the evening programme at Arthur Ashe Stadium, as 45-year-old Venus Williams plays 11th seed Karolina Muchova as she continues her age-defying return to the court.
The seven-times major champion became the oldest WTA match winner since 2004 at the Washington Open last month and earned a wild card entry into the Grand Slam where she has twice lifted the trophy.
"I want to be my best, and that's the expectation I have for myself, to get the best out of me. And that's all any player can ask for," said Williams.
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