Williams failed to raise her game against the Russian teen
Dinara Safina and Venus Williams both suffered shock defeats at the second-round stage of the China Open.
World number one Safina made 20 unforced errors and 12 double faults en route to a 7-5 7-6 (7-5) defeat by local wild card Zhang Shuai.
American Williams was beaten 3-6 6-1 6-4 by Anastasia Pavlyuchenkova - her second loss to the Russian in a week.
In the men's event, Serbian world number four Novak Djokovic beat Victor Hanescu of Romania 6-3 7-5.
Djokovic struggled to find his form in the match blaming jet lag for his below-par performance.
"That's the first round, you have to get used to the ups and downs," said the 22-year-old.
"I am aware I need to raise my level of performance to get far in the tournament.
"I'll have a rest tomorrow. I'm still a bit jet-lagged, I think you could see that in the second set."
Top seed Rafael Nadal will play his opening match against wild card Marcos Baghdatis on Tuesday. Both players are former winners of the event.
Nadal has a perfect 11-0 record in Beijing, having won the title in 2005 and the Olympic Games gold medal in 2008.
Twelve double faults didn't help me today - I wasn't counting those, though
In the women's competition, Serena Williams just needs to beat her second-round opponent Ekaterina Makarova in order to reclaim the world number one spot from Safina, who left the court in tears following her defeat to the world 226.
Double faults blighted Safina's display and also the performance of Venus Williams.
The world number three was made to struggle again by 18-year-old Pavlyuchenkova, who beat her in Tokyo last Monday.
"She played really well, unfortunately sometimes I made errors too soon in the play," said the 29-year-old.
"Twelve double faults didn't help me today, I wasn't counting those, though."
Belgian Yanina Wickmayer, a semi-finalist at the US Open, was beaten 5-7 6-3 6-3 by Russian Alisa Kleybanova.