An upset looked on the cards at the interval with Spurs 2-0 up thanks to an opportunist strike from Darren Bent and a neat control and finish from Luka Modric.
United grabbed a lifeline in the 57th minute when Ronaldo held his nerve to convert from the spot after keeper Heurelho Gomes and brought down Michael Carrick.
And after Rooney had slotted the equalised past Gomes at his near post in the 67th minute, the visitors crumbled.
Ronaldo headed a third from a Rooney cross a minute later and the England striker adding a fourth just three minutes after that.
Dimitar Berbatov poked home number five after the sorry Gomes spilled his initial header.
Liverpool had earlier kept up the pressure on Ferguson's men with a comfortable 3-1 win against 10-man Hull at the KC Stadium.
Xabi Alonso's strike and a Dirk Kuyt brace secured the victory which put Rafael Benitez's side temporarily ahead of United on goal difference.
Alonso scored on the stroke of half-time, hitting his free-kick straight into the wall but then lashing the rebound into the roof of the net, and after Caleb Folan had been sent off on the hour for a challenge on Martin Skrtel, Kuyt doubled the Reds' advantage with a header from a goalmouth scramble.
Geovanni pulled one back for Hull with 18 minutes to go, but
Kuyt volleyed home his second a minute from time to leave the Tigers in 17th place, three points above the drop zone.
Third-placed Chelsea kept in touch with the leaders with a 1-0 win at West Ham.
After dominating the first half, the Blues broke the deadlock 10 minutes after the break, Salomon Kalou controlling Frank Lampard's cross and rifling it past Robert Green.
Petr Cech responded to his recent critics by saving a second-half penalty from Mark Noble.
Fulham continued to look good in the race for a Europa League spot, moving back into seventh with victory over Stoke.
Erik Nevland scored the Cottagers' winner on the half hour, playing a one-two with Andy Johnson before slotting the ball coolly past Thomas Sorensen.
Robinho netted his second goal in two matches as Manchester City secured a rare away win, triumphing 2-1 at FA Cup finalists Everton.
The Brazilian put City ahead in the 35th minute, firing through Tim Howard's legs and then turned provider just after half-time, sending in a cross for Stephen Ireland to finish before Dan Gosling's late consolation for the hosts.
At the other end of the table, Sunderland's hopes of moving further away from the drop zone were dealt a blow at the Hawthorns with a 3-0 defeat against bottom side West Brom.
The Baggies went ahead against the run of play in the first half through Jonas Olsson, but further strikes from Chris Brunt and on-loan midfielder Juan Carlos Menseguez gave Tony Mowbray's side a comprehensive win which keeps them in with a mathematical chance of avoiding relegation.
Elsewhere, Aston Villa looked had looked set to ease their recent slump in form after Ashley Young's goal capped a decent first-half display at Bolton.
But Tamir Cohen's equaliser on the hour means it finished 1-1, extending Villa's winless run to nine league games.