Carlos Tevez (2) and Rio Ferdinand scored the other goals to help the champions overtake Arsenal in the title race after the Gunners were surprisingly held to a 1-1 draw at home by Birmingham City.
Like Arsenal, Manchester United have 51 points from 22 matches, but have a superior goal difference of plus-33 compared to the London club's plus-26.
Chelsea beat Tottenham Hotspur 2-0 to move on to 47 points from 22 games.
With 16 matches to play, the top three have pulled clear of fourth-placed Liverpool, who lead a quartet of clubs including Everton, Aston Villa and Manchester City on 39 points.
All six United goals came in the second half, with Ronaldo and Tevez putting the Reds on their way to their 10th successive home league win against their mid-table opponents who sacked manager Sam Allardyce on Wednesday.
Ronaldo scored his second of the match, and his 50th league goal for the club, to complete a well-worked move after 70 minutes with Rio Ferdinand making it 4-0 five minutes from time.
Ronaldo made it 5-0 and Tevez added his second in stoppage time to make it 6-0 before Newcastle's Alan Smith was red-carded for protesting about Tevez's second goal that barely crossed the line after bouncing down off the bar.