Serena Williams was ousted by Marion Bartoli 6-3, 7-6 (6), cutting short her return to Grand Slam tennis after nearly a year out with serious health problems, while Wozniacki was beaten by 24th-seeded Dominika Cibulkova of Slovakia 1-6, 7-6 (5), 7-5.
Venus Williams' attempt to win a sixth Wimbledon title ended with a 6-2, 6-3 loss to Tsvetana Pironkova of Bulgaria.
"Definitely not our best day," Venus said. "I think we both envisioned seeing this day going a little bit different."
The 23-year-old Pironkova beat Williams at Wimbledon last year by the same score to reach her first Grand Slam semifinal. She also won their first-round match at the Australian Open in 2006.
Venus and Serena have won nine of the last 11 titles at Wimbledon, and have faced each other in four finals.
In 2006, Venus lost in the third round and Serena missed the tournament. This is the first year that, when both sisters were in the draw, both lost before the quarterfinals.
The last time the sisters lost on the same day at a Grand Slam was in 2008, when they fell in the third round at the French Open.
"Obviously it's not something planned," Venus said. "We rarely lose on the same day."
For Wozniacki, Monday's loss extends her streak of never reaching the quarterfinals at Wimbledon. She is still searching for her first Grand Slam title.
"I don't really care what people think or say or do," she said. "I cannot really do anything now. I did my best and it wasn't good enough."
Wozniacki was the first to admit that she had herself to blame for failing to reach the Wimbledon quarterfinals for the first time.
The Dane breezed through the first set in only 24 minutes, and was up a break in the third, leading 2-0. But she was broken three times the rest of the way in a seesaw decider, including going down 6-5. Cibulkova then served out the match, converting her third match point with a forehand winner.
"It's kind of disappointing because when you're up 2-love with a break and have a lot of break points that you don't convert, that's kind of your own fault," Wozniacki said. "I was there. I should have taken my chance."
Serena, a four-time winner at the All England Club, saved four match points before the ninth-seeded Frenchwoman closed out the contest by hitting a service winner into the corner. It was Williams' earliest exit at Wimbledon since a third-round loss in 2005.
Serena missed nearly a year after foot surgery and subsequent blood clots in her lungs. She returned two weeks ago at Eastbourne for the first time since winning the Wimbledon title in 2010.
Serena had 20 unforced errors Monday to go with 29 winners, and managed to convert only one of five break points. Bartoli served 10 aces, two more than Williams, and kept down her errors to 17.
"I never came here thinking I would lose," she said. "That's my attitude. You win some and you lose some. Today just happened to be the one that slipped under me."
But Serena said she was satisfied getting as far as she did after such a long time away from the game.
"I think I did really well just being able to come back and play and win some matches, and just really play tough," she said. "Even today I lost, but I was able to kind of hang in there and play tough. And I can only get better. That can potentially be really scary, because I can only go up from here and I can just do so much more."
It was the first time Bartoli has beaten the American after straight-set defeats in their previous two matches. She reached the Wimbledon final in 2007, losing to Serena's older sister Venus.
"Beating Serena is almost like a dream come true," Bartoli said. "Even though she didn't play for almost one year, she's probably one of the greatest champions in women's tennis.
"For me to be able to come back after having three match points and losing this game at 6-5, and still be able to bounce back, it's really huge."
Venus was clearly off the top of her game Monday, committing 16 unforced errors and converting only one of four break points. She was broken four times.
"I didn't seem to get the ball in," Venus said. "She took her opportunities. I just didn't put the ball in the court, simple as that. Unfortunately, I seem not to have my good days against her. But she played well."
The 33rd-seeded Pironkova, who lost in the semifinals here last year to eventual runner-up Vera Zvonareva, played steady tennis against Venus and never cracked.
"I beat her two times, two consecutive years -- it feels amazing to play such a champion on this legendary court," the Bulgarian said after holding serve and stroking a backhand winner down the line on her second match point. "When I come here I just feel so relaxed. I really like the atmosphere here."
Azarenka became the first player to reach the quarterfinals, beating Nadia Petrova 6-2, 6-2.
The Belarusian equaled her previous best performance at the All England Club, where she made it to the quarters in 2009 before losing to Serena Williams.
Sharapova advanced by beating Peng Shuai of China 6-4, 6-2.
The fifth-seeded Russian, who won the 2004 title at the All England Club, broke for the first time to take a 5-4 lead in the first set Monday. From that break, she won seven straight games to take control.
Sharapova has also won the U.S. Open and Australian Open, but has only recently returned to top form after shoulder surgery in 2008.
"Last year I lost in the fourth round to Serena and this year I find myself in the quarterfinals and I'm giving myself an opportunity to go even in further so I'm quite happy about that," Sharapova said. "I have to be a little realistic about the fact that I haven't gotten past the fourth round in a few years. This is a step forward."
Sharapova will next face Cibulkova.
In other women's play, German wild card Sabine Lisicki reached the quarters for the second time, downing Petra Cetkovska 7-6 (3), 6-1; No. 8 Petra Kvitova, a semifinalist here last year, needed just 45 minutes to defeat No. 19 Yanina Wickmayer 6-0, 6-2; and 80th-ranked Austrian Tamira Paszek beat Ksenia Pervak of Russia 6-2, 2-6, 6-3 to secure her first Grand Slam quarterfinal berth.
Information from The Associated Press was used in this report.