The American star made it 19 straight prevails upon Sharapova with a 6-1, 6-1 thrashing at Arthur Ashe Stadium.
Williams, back at the US Open after her meltdown during her loss to Naomi Osaka in a year ago's conclusive, was in mind-boggling form, winning in only 58 minutes in New York.
The 37-year-old – hoping to approach Margaret Court's record of 24 grand slams – showcased her usual power yet committed a couple of errors in what was a prevailing showcase.
After a high caliber and serious begin, Williams – giving no indications of the back injury that saw her resign during the Rogers Cup final – handled the first blow, breaking in the fourth game when Sharapova sent a strike into the net.
Williams looked in brilliant form and another strike mistake from Sharapova saw her race into a 5-1 lead while in transit to taking the opening set.
Sharapova had few answers to Williams' power and accuracy, the last controlling through in style.
Williams, the eighth seed, will confront American Caty McNally in the second round.