It is the first time since 1990 the 49ers have gone 4-0 as they remain one of only two teams still to boast a 100 per cent record this campaign, along with the New England Patriots (5-0).
The Browns proved second best from the outset, with 49ers running back Matt Breida running in an 83-yard touchdown on San Francisco's opening play.
It was Breida's first score of the season, and his second came soon after with a five-yard touchdown catch on third-and-goal for a 14-0 lead.
By half-time, the home side racked up 185 rushing yards, the final 19 of which came on Tevin Coleman's first touchdown of the campaign, and went into the break with a 21-3 lead.
San Francisco added a fourth score in the third quarter through George Kittle to wrap up the win.
Cleveland, whose only points came from a Austin Seibert field goal, were unable to close the gap as they fell to 2-3.