Pavlyuchenkova began her 2016 season at the Brisbane International, reaching the quarterfinals by beating fifth seed Timea Bacsinszky and Alizé Cornet. There, she fell to eventual runner-up Angelique Kerber. The following week in Sydney, she lost to Karolína Plíšková in the second round. She then suffered a second consecutive first round loss at the Australian Open when she fell to Lauren Davis in her opening match. She then reached the quarterfinals on home soil in St. Petersburg after seeing off Klára Koukalová and Carina Witthöft but there, she was beaten by eventual runner-up Belinda Bencic. She then made the quarterfinals in Acapulco where she lost to Yanina Wickmayer, but then suffered her first ever opening-round defeat in Monterrey where she lost to Pauline Parmentier in straight sets.