Mason - Eighth seeded Petra Kvitova used her precision serve to overpower Serena Williams 6-3, 2-6, 6-3 in their second round match on Tuesday night in Cincinnati.
The 23-time Grand Slam champion won her first round match over Daria Gavrilova in straight sets, 6-1, 6-2, on Monday, but appeared to run out of gas in the third set against Kvitova.
Just two weeks ago, Williams suffered the worst defeat of her career in San Jose when she was crushed 6-1, 6-0 in 51 minutes by world No 39 Johanna Konta.
"I'm still at the very beginning. You know, this is a long comeback. I just began. Definitely at the very, very beginning," Williams said.
"I'm getting there, and I'm going to just continue to work hard, and hopefully I'll start winning more matches."
Czech ninth seed Karolina Pliskova made a personal breakthrough as she beat Agnieszka Radwanska for the first time after seven previous straight-sets losses to the Pole, winning 6-3, 6-3.
"It was a tough round for me because I've never beaten her, never even taken a set," said Pliskova.
"I was so happy when I won the first set because I thought, 'Finally, one set for me.'"
Australian 16th seed Ashleigh Barty defeated Czech teenager Ma Marketa Vondrousova 6-3, 7-5, while 14th-ranked Elise Mertens topped Magdalena Rybarikova 6-4, 6-2.
Results from the ATP and WTA Cincinnati Masters tournament on Tuesday (x denotes seeding):
Leonardo Mayer (ARG) bt Lucas Pouille (FRA x16) 7-6 (9/7), 6-4
Roger Federer (SUI x2) bt Peter Gojowczyk (GER) 6-4, 6-4
Denis Shapovalov (CAN) bt Kyle Edmund (GBR x14) 6-4, 7-5
Milos Raonic (CAN) bt Dusan Lajovic (SRB) 6-3, 6-3
Robin Haase (NED) bt Filip Krajinovic (SRB) 4-6, 6-2, 6-3
Karen Khachanov (RUS) bt Albert Ramos-Vinolas (ESP) 2-6, 6-3, 6-2
Marius Copil (ROU) bt Philipp Kohlschreiber (GER) 6-4, 6-2
Nick Kyrgios (AUS x15) bt Denis Kudla (USA) 6-7 (2/7), 7-5, 7-6 (11/9)
Borna Coric (CRO) bt Daniil Medvedev (RUS) 6-2, 6-3
Chung Hyeon (KOR) bt Jack Sock (USA) 2-6, 6-1, 6-2
David Goffin (BEL x11) bt Stefanos Tsitsipas (GRE) 7-5, 6-3
Marton Fucsovics (HUN) bt Hubert Hurkacz (POL) 4-6, 6-3, 7-6 (8/6)
Mischa Zverev (GER) bt Damir Dzumhur (BIH) 6-3, 6-4
Kristina Mladenovic (FRA) bt Viktoria Kuzmova (SVK) 6-3, 6-0
Caroline Garcia (FRA x6) bt Victoria Azarenka (BLR) 6-4, 7-5
Petra Kvitova (CZE x8) bt Serena Williams (USA) 6-3, 2-6, 6-3
Elina Svitolina (UKR x5) bt Svetlana Kuznetsova (RUS) 7-6 (7/1), 4-6, 6-4
Kaia Kanepi (EST) bt Varvara Lepchenko (USA) 2-6, 6-3, 6-1
Ashleigh Barty (AUS x16) bt Marketa Vondrousova (CZE) 6-3, 7-5
Ekaterina Makarova (RUS) bt Ana Bogdan (ROU) 6-3, 6-2
Anastasia Pavlyuchenkova (RUS) bt Aleksandra Krunic (SRB) 6-1, 6-0
Camila Giorgi (ITA) bt Anastasija Sevastova (LAT) 6-2, 6-3
Karolina Pliskova (CZE x9) bt Agnieszka Radwanska (POL) 6-3, 6-3
Elise Mertens (BEL x15) bt Magdalena Rybarikova (SVK) 6-4, 6-2
Tatjana Maria (GER) bt Alexandra Kiick (USA) 5-7, 6-3, 6-3
Amanda Anisimova (USA) bt Timea Babos (HUN) 6-3, 6-4
Maria Sakkari (GRE) bt Naomi Osaka (JPN) 6-3, 7-6 (10/8)
Kiki Bertens (NED) bt CoCo Vandeweghe (USA) 6-2, 6-0
Petra Martic (CRO) bt Darya Kasatkina (RUS x12) 4-6, 6-4, 6-3