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Sharapova raced to victory over the 31-year-old Dominguez Lino in just 54 minutes with the Spaniard unable to hit a single winner in the brutally one-sided clash.
The 2006 champion next faces American college player Mallory Burdette, the world number 252 who studies psychology at Stanford and is making her Grand Slam debut.
"It's a big stage for her. She will have the home support behind her. She will be a difficult opponent," said Sharapova.
Sharapova has dropped just five games in her first two matches at the US Open as she looks to add the New York title to the French Open she captured in June.
The Russian fired 30 winners past the World No 78 and accounted for 17 of her opponent's 24 points through unforced errors.
Results from the third day of the US Open on on Wednesday (x denotes seeding):
Men
First round
Janko Tipsarevic (SRB x8) bt Guillaume Rufin (FRA) 4-6, 3-6, 6-2, 6-3, 6-2
Brian Baker (USA) bt Jan Hajek (CZE) 6-3, 6-4, 6-2
Grega Zemlja (SLO) bt Ricardo Mello (BRA) 7-5, 7-6 (7/3), 7-5
Cedrik-Marcel Stebe (GER) bt Viktor Troicki (SRB x29) 6-4, 6-4, 3-6, 6-2
Benoit Paire (FRA) bt Grigor Dimitrov (BUL) 5-7, 6-3, 7-6 (7/4), 6-2
Jarkko Nieminen (FIN) bt Mikhail Kukushkin (KAZ) 6-0, 6-2 - retired
John Isner (USA x9) bt Xavier Malisse (BEL) 6-3, 7-6 (7/5), 5-7, 7-6 (11/9)
Richard Gasquet (FRA x13) bt Albert Montanes (ESP) 4-6, 6-2, 6-3, 6-3
Gilles Muller (LUX) bt Mikhail Youzhny (RUS x28) 2-6, 3-6, 7-5, 7-6 (8/6), 7-6 (8/6)
Lleyton Hewitt (AUS) bt Tobias Kamke (GER) 4-6, 6-2, 6-1, 6-4
Igor Sijsling (NED) bt Daniel Gimeno (ESP) 7-5, 6-3, 6-4
David Ferrer (ESP x4) bt Kevin Anderson (RSA) 6-4, 6-2, 7-6 (7/3)
Leonardo Mayer (ARG) bt Lukasz Kubot (POL) 6-4, 6-4, 7-5
Juan Martin del Potro (ARG x7) bt Florent Serra (FRA) 6-4, 7-6 (7/4), 6-4
Steve Johnson (USA) bt Rajeev Ram (USA) 6-3, 7-6 (7/5), 6-3
Tommy Robredo (ESP) bt Andreas Seppi (ITA x26) 6-1, 7-5, 6-3
Ernests Gulbis (LAT) bt Tommy Haas (GER x21) 3-6, 4-6, 6-4, 7-5, 6-3
Ryan Harrison (USA) bt Benjamin Becker (GER) 7-5, 6-4, 6-2
Philipp Kohlschreiber (GER x19) bt Michael Llodra (FRA) 7-6 (7/2), 4-6, 7-6 (7/4), 6-1
Bradley Kahn (USA) bt Jurgen Melzer (AUT) 4-6, 6-3, 7-5, 5-7, 6-4
Women
Second round
Victoria Azarenka (BLR x1) bt Kirsten Flipkens (BEL) 6-2, 6-2
Zheng Jie (CHN x28) bt Magdalena Rybarikova (SVK) 6-3, 6-1
Mandy Minella (LUX) bt Kristyna Pliskova (CZE) 6-4, 6-4
Li Na (CHN x9) bt Casey Dellacqua (AUS) 6-4, 6-4
Varvara Lepchenko (USA x31) bt Anastasia Rodionova (AUS) 6-2, 6-2
Mallory Burdette (USA) bt Lucie Hradecka (CZE) 6-2, 6-4
Nadia Petrova (RUS x19) bt Simona Halep (ROM) 6-1, 6-1
Lucie Safarova (CZE x15) bt Aleksandra Wozniak (CAN) 6-3, 4-6, 6-2
Pauline Parmentier (FRA) bt Yanina Wickmayer (BEL x25) 7-6 (7/5), 6-3
Petra Kvitova (CZE x5) bt Alize Cornet (FRA) 6-4, 6-3
Laura Robson (GBR) bt Kim Clijsters (BEL x23) 7-6 (7/4), 7-6 (7/5)
Anna Tatishvili (GEO) bt Sorana Cirstea (ROM) 6-7 (5/7), 6-1, 6-2
Kristina Mladenovic (FRA) bt Anastasia Pavlyuchenkova (RUS x17) 6-1, 6-2
Samantha Stosur (AUS x7) bt Edina Gallovits-Hall (ROM) 6-3, 6-0
Maria Sharapova (RUS x3) bt Lourdes Dominguez Lino (ESP) 6-0, 6-1
Marion Bartoli (FRA x11) bt Romina Oprandi (SUI) 6-1, 1-6, 7-5
