Dominic Thiem, who beat Roger Federer recently to win the Indian Wells title, got knocked out by Polish 22-year-old Hubert Hurkacz in the second round of the Miami Open.
Thiem lost the match 4-6, 4-6.
Meanwhile, world number one Novak Djokovic advanced into the third round.
In the women's section, there were victories for Naomi Osaka and the Williams sisters.
Djokovic beats Tomic, Isner wins a thriller
Djokovic moved on from the Indian Wells disappointment with a ruthless 7-6, 6-2 win against Australian Bernard Tomic.
The Serb hit 11 aces and dominated the show with his first serve.
Djokovic is eyeing a record seventh title in South Florida.
Meanwhile, Kei Nishikori lost to Serbian Dusan Lajovic 6-2, 2-6, 3-6.
Reigning champion John Isner overcame Italian qualifier Lorenzo Sonego 7-6, 7-6.
Now hopefully, I can build some momentum: Djokovic
"I commonly feel like that. This was my first time playing at this new stadium, it felt like being indoor a little bit. It's unique. Now hopefully, I can build some momentum," said Djokovic.
Osaka survives scare against Wickmayer
Women's singles world number one Naomi Osaka survived a scare to overcome Yanina Wickmayer 6-0, 6-7 (3/7), 6-1.
Osaka lost her way in the middle, but came back strongly against 141st-ranked Wickmayer.
"In the second set, I got really emotional, so in the third, I just tried to shut off my feelings. I started thinking about winning," Osaka said.
Serena makes it against Peterson, Venus progresses
Serena battled past Sweden's Rebecca Peterson 6-3, 1-6, 6-1.
She will now come up against China's Wang Qiang, who thrashed Britain's Jo Konta 6-4, 6-0.
"I wasn't really happy with my performance," admitted the veteran Serena.
She is in her third tournament in 2019.
Meanwhile, in-form Venus Williams advanced with a 7-6, 6-1 win over Spain's Carla Suarez Navarro.
In-form teenager Andreescu to face Kerber
Bianca Andreescu, who beat Angelique Kerber to win the Indian Wells title, will meet her once again in the third round of the Miami Open. Andreescu overcame Sofia Kenin 6-3, 6-3. Meanwhile, Germany's Kerber edged past Karolina Muchova 3-6, 6-3, 6-3.