CoCo Vandeweghe went out next as things really started to go crazy for the U.S. women, who eventually lost nine out of 10 first-round matches on a bleak opening day of the Australian Open.
Four months after American women filled all four semifinal spots at the US Open -- for the first time in 36 years -- three of them are out of contention at the next Grand Slam.
In her first match at Rod Laver Arena since a vintage run in 2017 ended in a championship loss to sister Serena, Venus Williams lost her opener to Belinda Bencic 6-3, 7-5 to ensure the title won't stay in the family.
Serena Williams hasn't played a Grand Slam tournament since winning her 23rd major in Australia last year. She has taken time off because of her pregnancy and the birth of her first child.
Fifth-seeded Venus was considered a serious contender in her 77th major to break a Grand Slam title drought dating back to 2008.
Bencic, who had never won a set against Venus in four previous matches and had lost to Serena in the first round last year, had other ideas.
"I think I had a little bit too much respect, played a little bit careful and safe," Bencic said of her four previous losses to Venus. "This time I really tried to come out and hit it big."
Bencic saved five break points in the eighth game before a rain delay caused an almost half-hour suspension of play as the roof was closed on Rod Laver Arena. She returned on a roll, winning the next six points to clinch the first set, and then dominated the second.
Venus had 26 unforced errors and 22 winners, and said she didn't get the luck of the draw by having to play somebody who has been ranked as high as No. 7.
"I don't think I played a bad match. She just played above and beyond," Williams said. "I just have to give her credit for that."
Bencic, 20, who was born a couple of months after the last time there was no Williams in the second round at the Australian Open (1997), hit 32 winners, had 12 unforced errors and converted five of 11 break-point chances.
She credited playing with Roger Federer at the Hopman Cup -- where they teamed up to win for Switzerland -- with helping her recent improvement. Having Federer's parents supporting her in the crowd also helped.
Stephens was the first American to falter, losing 2-6, 7-6 (2), 6-2 to No. 34-ranked Zhang Shuai to extend her losing streak since the US Open to eight matches.
"Tennis is definitely a roller coaster," said the 13th-seeded Stephens, who was broken while serving for the match in the second set. "But I have learned to just not panic. It will be OK."
It wasn't OK for the 10th-seeded Vandeweghe, a semifinalist in Melbourne and at the US Open last year, who was feeling sick and frustrated in a 7-6 (4), 6-2 loss to Timea Babos.
She yelled an obscenity late in the second set, and then got a time violation for waiting too long for a banana to be brought to the court between sets, earning a point penalty.
"I was just trying to wait for what I asked for to come and the chair umpire deemed that it wasn't a good enough reason," she said.
CiCi Bellis, Sofia Kenin -- who lost to No. 12 Julia Goerges, now on a 15-match winning streak -- Alison Riske, Taylor Townsend and Jennifer Brady all lost before Nicole Gibbs beat Viktoriya Tomova 6-1, 6-1 to end the streak of eight losses for the U.S. women.
"Yes we were talking about it in the locker room and some of them were ribbing me that I had to carry the flag for us," Gibbs said. "It was a tough day, and this is a tough sport. This isn't an indication of anything except we have a lot of depth and we had a bad day."
French Open champion Jelena Ostapenko started with a 6-1, 6-4 win over 37-year-old Francesca Schiavone, the 2010 French Open winner. Olympic gold medalist Monica Puig saved a match point before recovering for a win over former US Open champion Sam Stosur.
Information from The Associated Press was used in this report.