The British Open champion, who rarely looked like dropping a shot all day, had to survive a nervy finish when he hit a poor drive then landed his second in the bunker at the 18th.
However, he splashed out gently from the sand to leave himself with an easy par putt to cap another bogey-free round.
"Played the back nine probably as good as I've ever played over here, so really pleased about that. And then obviously a good save on 18," said Molinari, whose only bogey at the tournament came in the first round.
"So nice to keep another clean scorecard."
The world number seven, who has improved all week after rounds of 70 and 67, has a two-stroke lead on Tony Finau and Tiger Woods.
The trio will tee off together earlier than originally scheduled, after tournament organisers pushed forward the play schedule due to expected hazardous weather.
"Obviously it's nice to be a little bit ahead, but you might just need one hole to change," Molinari said. "You never know how it's going to go, especially around a course like here."
If Molinari takes home the Green Jacket, it would mark something of a fairytale finish for the 36-year-old Italian, who first arrived at Augusta National in 2006 as a caddie for his older brother, Edoardo, in 2006.
(Editing by Peter Rutherford)
