Sassuolo make a mess of clearing their lines from a corner, with the ball rebounding kindly to Ronaldo off the post for the 33-year-old to tap into an empty net.
Sassuolo pulled a goal back in stoppage time but Juventus held on to record their fourth straight win of the league campaign.
Juventus, who are seeking a record-extending eighth successive Serie A title, are the only team in the division still with a flawless record.
Douglas Costa was then sent off after spitting at Federico di Francesco, with the Brazilian winger also appearing to aim a headbutt and elbow his opponent.
With his first brace in Serie A, Ronaldo has gained his 400th league goal making him only the fifth player in history to reach such milestone. "I really wanted to score, so I'm happy".
"So there were a lot of expectations, but I thank my teammates for supporting me throughout. The media are the first to demand he plays and then tear him apart when he does".
Roma was made to pay for its complacency as it fumbled a two-goal lead to draw 2-2 against Chievo Verona.
Sassuolo allowed Ronaldo few openings in the first half apart from an early shot which was blocked and a header wide from Alex Sandro's cross.
Winless Chievo are on minus one point after having three deducted on Thursday by the Italian federation over accounting irregularities.
Ronaldo was delighted to get off the mark for his new club.