The US' Sofia Kenin lost her first WTA match since winning the Australian Open earlier this month as she went down 6-7 (2/7), 6-3, 6-3 to Elena Rybakina on Tuesday at the Dubai Championships.
World number seven Kenin's loss completed a hat-trick of seeded upsets on the fourth day of action in the United Arab Emirates.
Title holder Belinda Bencic was overhauled 1-6, 6-1, 6-1 by Anastasia Pavlyuchenkova while third seed and two-time tournament winner Elina Svitolina was hammered 6-2, 6-1 by qualifier Jennifer Brady.
Kenin played a pair of non-Tour Fed Cup matches immediately after her Melbourne win over Garbine Muguruza, who cut short Kim Clijsters' comeback on Monday.
The 21-year-old went down in just over two hours to her 19th-ranked opponent who stood 192nd in the world a year ago.
Kenin got away to an early break but lost it and had to win the first set in a tiebreaker. Rybakina then dominated the next two sets to reach the second round where she will face Russian Katerina Siniakova.
Kazakh Rybakina won the Hobart title in January and reached the final last weekend in St Petersburg.
"I prepared with good practice. I didn't expect that I would win. I tried to do my best," she said.
"I wasn't nervous (after flying here from Russia) at all because I knew it's going to be tough.
"I didn't think about that she just won the Australian Open, I know that now everyone can beat everyone," she added.
- Bencic burns -
Earlier, Bencic ran off the first 19 points against Anastasia Pavlyuchenkova before collapsing to a 1-6, 6-1, 6-1 loss.
Pavlyuchenkova could not have made a worse start before advancing in 92 minutes.
"It's tennis, sometimes it happens," the 31st-ranked Russian said.
"You go out there and you just don't feel anything. I just kept on fighting, still trying to hit every ball, trying to be there.
"Slowly I started to turn it around, I started to find my game. In the third set, it was a good level from both of us."
The shock defeats leaves the spotlight to tournament number one Simona Halep and second-seeded Karolina Pliskova, who begin in the second round after byes.
Weekend ATP Rotterdam winner Gael Monfils watched in pain as girlfriend Svitolina went down to Brady.
Svitolina had little to offer as the 52nd-ranked Brady gained her second victory this season over a Top 10 opponent after beating Ashleigh Barty in Brisbane.
The Ukrainian's usually steady game was nowhere to be found at the Aviation Club as first-round play concluded.
"It was not a bad start, but then everything just went downhill," Svitolina said.
"I wish I could regroup better. In the end, I didn't feel so good the ball. Just everything was all over the place today.
"Before I was more composed with my game. Now it's little bit of a struggle. Maybe mentally or something."
Brady, a qualifier with three matches already here, said her own attitude as the underdog may have helped.
"I'm respecting my opponent, but not to the point where I put her on a pedestal.
"I was just focused on my game plan, myself, I competed well from the very beginning.
"From the start, maybe she felt my presence. I was happy with the way I performed."
Frenchwoman Kristina Mladenovic beat fellow qualifier Aliaksandra Sasnovich 6-4, 6-3 to set up a second-round date with Pliskova.
Sofia Kenin was born in Russia before moving to the US as a child
Fighting back: Anastasia Pavlyuchenkova lost the first 19 points but beat Belinda Bencic