Sabalenka is aiming to become the first woman since Serena Williams in 2014 to successfully defend the singles title in New York.
She has reached at least the last four in each of the three Grand Slams so far this season, losing the finals of both the French and Australian Open.
But the three-time Grand Slam singles champion arrived at Flushing Meadows on the back of an unconvincing Cincinnati Open display, where she scraped past Emma Raducanu before losing to Elena Rybakina.
In an uneasy start, Sabalenka was broken in the fifth game of the first set by Masarova, before responding immediately to level at 3-3.
It remained on serve until Sabalenka earned a set point at 6-5 up – one which Masarova thought she had saved, only for the top seed to produce a stunning defensive return to the Swiss’s overhead smash.
It forced Masarova into a lobbed return, which Sabalenka sent crashing down the line with a roar to take the first set.
Masarova, the world number 108, was deflated from there on and held serve just once in the second set as Sabalenka raced to victory.
“I feel like I didn’t start my best in the first games, but then I found my rhythm,” Sabalenka said.
The Belarusian will face Polina Kudermetova next, the Russian advancing after opponent Nuria Parrizas-Diaz of Spain retired with injury.