Pavlyuchenkova opened her 2011 season as the 5th seed in Brisbane. Despite being pushed to three sets in two prior matches, she managed to reach the semifinals, where she fell to eventual champion Petra Kvitová. The following week, in Hobart, Pavlyuchenkova was forced to retire in the opening round against Bethanie Mattek-Sands, already having lost the first set 6–2. At the Australian Open, she advanced to the third round, losing to Iveta Benešová in a tight three-set match, 3–6, 6–1, 5–7.
In Fed Cup competition, Pavlyuchenkova helped Russia rally from an 0–2 deficit against France by winning her reverse singles match against Alizé Cornet and tie-deciding doubles match, partnering with Svetlana Kuznetsova.
In her next tournaments in the Middle East, she would have to play qualifying because of failing to meet the main entry deadline; she qualified for Dubai, but fell in the first round to fellow Russian Alisa Kleybanova in three sets.
In early March she defended her title at the 2011 Monterrey Open, defeating Jelena Janković 2–6, 6–2, 6–3. She would reach the third round of the 2011 BNP Paribas Open, losing to 10th seed Shahar Peer. That was followed by a 4th round loss to 8th seed and eventual champion Victoria Azarenka in three sets at the 2011 Sony Ericsson Open in Miami.
Pavlyuchenkova would begin her clay-court season with a run to the 4th round at the 2011 Porsche Tennis Grand Prix in Stuttgart, where she lost to 2nd seed Vera Zvonareva. She then reached the quarterfinals of the 2011 Mutua Madrid Open, losing to Julia Goerges. At the 2011 Internazionali BNL d'Italia, Pavlyuchenkova would reach the 4th round, where she lost to 3rd seed Victoria Azarenka.
Pavlyuchenkova was the 14th seed at the 2011 French Open and reached her first ever Grand Slam quarterfinal, losing in three sets to #5 seed and defending champion Francesca Schiavone. At the 2011 Wimbledon Championships, Pavlyuchenkova was beaten in the second round 6–3, 6–3, by Nadia Petrova. Anastasia next played at the 2011 Baku Cup where she lost in the quarterfinals to Galina Voskoboeva 6–7, 6–3, 6–4 during the match, Pavlyuchenkova struck an incredible 27 double faults, effectively surrendering almost seven service games in double faults.
After defeating Anna Tatishvili, Petra Martić and former world number one Jelena Jankovic at the 2011 US Open, Pavlyuchenkova advanced to her second grand slam quarterfinal of the year after a 5–7, 6–3, 6–4 victory over seventh seed Francesca Schiavone. Pavlyuchenkova lost to Serena Williams 7–5, 6–1 in the quarterfinal. She was later fined US$2,000 by the USTA for improper coaching.
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