Wayne Rooney opened the scoring when he converted a right-wing cross from Wes Brown, before Rooney turned provider when he squared from the left for Louis Saha to volley home.
Cristiano Ronaldo added a third just before the break with a stunning free-kick before Saha rubbed salt into the wound with an 86th-minute penalty after Nani had been tripped by Danny Collins.
United headed back across the Pennines having reached the mid-point of the season firmly in the title race, two points clear of Arsenal who play later, while the man who for more than 12 years led their charge for glory on the pitch has just 14 points in the bag and a long haul towards safety.
Keane knows the bulk of his side's points this season will not be taken from the likes of United, Arsenal, Chelsea and Liverpool, but from the sides in the battle for top-flight survival.
However, having seen them compete creditably in narrow defeats at both Old Trafford and the Emirates Stadium already, that was the very least he expected at the Stadium of Light today.
What he got in the opening 45 minutes was graft and commitment, but what his players lack was abundantly clear as United, despite barely getting out of second gear, took them apart so comprehensively that damage limitation was the only thing on the minds of the bulk of a St Stephen's Day crowd of 47,360.
Despite leaving Ryan Giggs and Anderson at home and Carlos Tevez and Patrice Evra on the bench, Ferguson was able to field a side which had simply too much class, pace and guile for Keane's team, which included for the first time 17-year-old striker Martyn Waghorn.
Where Tomasz Kuszczak had only one save to make in the first-half when he tipped over Ross Wallace's 40th-minute drive, opposite number Craig Gordon was peppered throughout.
Had he not pulled off fine saves from two Ronaldo free-kicks and a Wes Brown header, United could have been six goals to the good by half-time.
As it was, they were 3-0 up courtesy of some scintillating passing and movement, as well as top-class finishing.
Rooney set the ball rolling on 20 minutes when, after full-back Brown had played a one-two with Ronaldo, he slid the striker in to fire nonchalantly past Gordon.
Rooney turned provider 10 minutes later, accepting Ronaldo's pass from the United half before cutting inside Wallace to pick out Saha at the near post.
But it was the Portugal international who set the seal on a blistering start when he smashed home an injury-time free-kick with Gordon rooted to the spot.
Keane's response was to replace Wallace with the more combative Grant Leadbitter and withdraw Waghorn into a five-man midfield for the second half, although the Black Cats were pinned back inside their own half as United threatened to cut loose.
There was a brief glimmer of hope for the home side when Michael Chopra's enterprising run set up Dickson Etuhu to shoot on 51 minutes, but he skied his effort harmlessly over.
Former United defender Paul McShane denied Rooney a second with a 54th-minute block, but Kuszczak had to dive low to his right to keep out Kenwyne Jones' 56th-minute strike.
Ronaldo departed to warm applause from both sets of supporters a minute later with his job done as Park Ji-Sung was handed his first taste of first-team action since undergoing knee surgery in March.
The home side rallied as the clock ran down, but with the visitors in cruise control, genuine openings were few and far between.
Chopra saw a 75th-minute shot beaten away by Kuszczak, but it came either side of another Gordon save from Rooney and an uncharacteristically wild close-range volley from the United man.
There was, however more to come, and when Nani went down under Collins' challenge, referee Uriah Rennie pointed to the spot and Saha obliged.