The American rarely put a foot wrong in the 1 hour and 6-minute contest, dominating in every area.
Williams, who has missed Cincinnati the last two years due to her pregnancy, ran her winning streak in Mason to 11 matches, having claimed the title in 2014 and 2015.
Firing 27 winners and eight aces, she sets up a blockbuster Round of 32 showdown with Petra Kvitova.
Williams comes out firing
It was a statement of intent right from the off for the 23-time Grand Slam champion, claiming a break in the opening game courtesy of a forehand winner.
A rare spate of errors gave Gavrilova her first and only game of the opening set, but soon thereafter it was Williams who was back in top gear, firing off another forehand winner for a 4-1 lead.
The Aussie blew a 40-15 lead in her next service game and once again it was the Williams forehand that sealed a second break of the first set for a 5-1 lead.
Serving for the set, the former world number one saved a break point to cap off a most impressive opening set.
Serena eases to victory to set up Kvitova clash
The second set was much like the first with Williams gaining an early advantage. After each player recorded a hold, it was the American with three break points and an errant backhand from Gavrilova handed her the lead.
It was more of the same in the fifth game with Williams holding three break points.
The world number 23 did well to save the first two, but a double fault on the third put the American in front 4-1, Gavrilova visibly frustrated.
Eventually, the match, which was never really in doubt for Williams ended when she fired an unreturnable serve past the overmatched Gavrilova to conclude what was easily her best performance since returning to the tour.