Azarenka left the tournament Wednesday due to a knee injury and a series of upsets have further opened the lower half of the draw. Sharapova lost to world No. 131 Michelle Larcher de Brito 6-3, 6-4 and Petra Cetkovska ousted ninth-seeded Caroline Wozniacki 6-2, 6-2.
Azarenka, Sharapova and Wozniacki join No. 5-seeded Sara Errani, who was eliminated in the first round Monday, on the sidelines -- leaving eighth-seeded Petra Kvitova, who won at Wimbledon in 2011, as the highest seeded player left in that half of the draw.
Kvitova moved into the third round when Yaroslava Shvedova withdrew prior to the match.
Azarenka defeated Maria Joao Koehler 6-1, 6-2 in the first round Monday but took a fall that left her writhing in pain. She met with a trainer after the fall early in the second set and had the injured right knee wrapped before finishing the win.
Her camp reported Tuesday there was no structural damage to the knee but minutes before Azarenka was to play Flavia Pennetta in the second round Wednesday, the Belarusian star withdrew.
Larcher de Brito had never before beaten a Top 10 player but dropped serve just once in taking out Sharapova. Sharapova had a pair of break chances in the final game but Larcher de Brito was able to advance on her fifth match point try.
In other upsets, local favorite Eugenie Bouchard delighted the British crowd with a 6-3, 6-3 win over 12th-seeded Ana Ivanovic; Vesna Dolonc took out 16th-seeded Jelena Jankovic 7-5, 6-2; Camila Giorgi held on for a 7-6 (9-7), 7-6 (8-6) win over 22nd-seeded Sorana Cirstea; and Karin Knapp rallied for a 4-6, 6-4, 6-4 decision over No. 27-seeded Lucie Safarova.
Marion Bartoli, the No. 15 seed, took a tight 7-5, 6-4 match over Christina McHale. Other seeded winners Wednesday included No. 17 Sloane Stephens, 19th-seeded Carla Suarez Navarro, 20th-seeded Kirsten Flipkens, No. 25 Ekaterina Makarova and No. 29 Alize Cornet.
Unseeded players going into the third round included Eva Birnerova and Monica Puig, who had handed Errani her first-round upset.