Ronaldo, whose mother used to complain that he never scores trebles, was the man of the game with dominant display in the midfield.
Carlos Tevez posted a double and stand-in captain Rio Ferdinand completed the rout.
The defending champions now have 51 points, level with Arsenal, but leading on one-goal difference.
Arsenal were held to a 1-1 draw by Birmingham at home earlier on the same day.
Chelsea also stayed in the hunt, as their 2-0 triumph over Tottenham left them third, just three points behind the joint leaders.
Newcastle played without a manager but managed to keep United at bay in the first period.
But the floodgates opened after the restart as Ronaldo's wicked free-kick opened the scoring in the 48th minute.
He anticipated the Newcastle wall will jump to block a high shot only to arrow a low drive from underneath.
Newcastle's sparkling keeper Shay Given made an attempt but the ball was too powerful to be parried.
Argentina striker Tevez doubled the lead in the 55th minute, converting Ryan Giggs' square pass home.
Giggs initially scuffed a loose ball after Given's clearance hit the back of a teammate.
Ronaldo stretched the lead with a fierce shot from inside the area after being set-up by Tevez in the 70th minute.
Ferdinand volleyed home in the 85th minute and Ronaldo produced another piece of magic before burying the fifth home three minutes later.
Tevez headed into the crossbar and his ball fell behind the goal line as United wrapped up a precious victory.