The Williams sisters were the biggest casualties to fall in an eventful fourth round, Serena losing to Marion Bartoli shortly before Venus was demolished by Tsvetana Pironkova.
Top seed and world No. 1 Caroline Wozniacki also bowed out, losing a nail-biting clash to Dominika Cibulkova 1-6 7-6 (7/5) 7-5.
The departures of three main contenders has cleared the path for Sharapova to reclaim the title she won in 2004.
The Russian saw off the challenge of China’s Peng Shuai to reach her first Wimbledon quarter-final in five years.
Slovakian 24th seed Dominika Cibulkova stands between her and a place in the last four with the rivals scheduled to meet on Centre Court this afternoon.
“I’m in the quarters here for the first time since 2006. It’s only going to get tougher from here,” said Sharapova, who beat Peng 6-4 6-2. Sharapova has lost to Cibulkova in their last two meetings.
Opening proceedings on Centre Court is Marion Bartoli’s clash with Sabine Lisicki. French ninth seed Bartoli looked highly impressive as she dispatched a battling Serena.
“I’m extremely happy about beating Serena, she’s extremely tough to beat,” she said.
“It was a great performance but this is another day so I have to stay extremely focused and not think too far ahead.”
Today’s remaining two quarter-finals, both on Court One, will force many to thumb through their Who’s Who of women’s tennis.
Fourth seed Victoria Azarenka of Belarus meets world No. 80 Tamira Paszek while Petra Kvitova, the eighth seed, faces Tsvetana Pironkova.
Pironkova, the 32nd seed, looked magnificent as she dispatched Venus Williams 6-2 6-3 for the second year in succession.