Mattek-Sands advanced to play fellow American Madison Keys, who defeated Croatian wild-card entry Ajla Tomljanovic 6-0, 3-6, 7-6 (3).
Former No. 1 Caroline Wozniacki was also on the receiving end of an upset, falling to Lucie Safarova 6-4, 7-6 (7). Wozniacki, recently engaged to golfer Rory McIlroy, was up three points in the second-set tiebreaker before allowing Safarova to clinch the match.
Former Wimbledon champion Petra Kvitova, the second seed, had little trouble in the afternoon session, beating American qualifier Christina McHale 6-1, 6-0. Angelique Kerber of Germany was also through to the quarterfinals after beating Kaia Kanepi of Estonia 6-3 6-4.
In men's play at Sydney, seventh-seeded Marin Cilic of Croatia defeated Jan-Lennard Struff of Germany 3-6, 6-3, 6-3, Spain's Albert Ramos took out American Sam Querrey 4-6, 6-3, 6-4, and Nicolas Mahut of France beat American Ryan Harrison 7-6 (2), 7-5.
At the ATP tournament at Auckland, New Zealand, American qualifier Donald Young beat Federico Delbonis of Argentina 7-5, 6-2 to set up a showdown with top seed David Ferrer. German Philipp Kohlschreiber, the fifth seed, and Frenchman Benoit Paire, the sixth seed, were also winners.
At the Hobart International WTA event, Australian teenager and wild-card entry Storm Sanders beat China's Peng Shuai, ranked nearly 200 places ahead of her, 6-2, 6-2. Sanders was only given a wild card when fellow Australian Ashleigh Barty withdrew with a hip injury.
American Alison Riske beat Australian Casey Dellacqua 7-5, 4-6, 6-3 in another second-round match, while defending champion Elena Vesnina of Russia advanced with a 6-4, 6-4 win over Monica Puig of Puerto Rico.
Lleyton Hewitt, meanwhile, withdrew from the Kooyong exhibition tournament in Melbourne, saying he feared playing would harm his preparations for the Australian Open.
The veteran Hewitt, who has struggled with injuries in recent years, reclaimed his place as Australia's top-ranked player when he won the Brisbane International on Sunday with a 6-1, 4-6, 6-3 upset victory over Roger Federer.
''At the moment it's just all about recovery for me,'' the 32-year-old said. ''When you get older it gets a bit tougher than when you were 16.''
Most of the top players have chosen to take the week off before the year's first Grand Slam and are training instead at Melbourne Park.