Yorke, 35, fired home his fourth goal of the season in the 23rd minute with a classy finish before Stern John added a second after 49 minutes to send Albion crashing to their first league defeat since New Year's Day at Southend United.
Albion only came to life after falling two behind and substitute Darren Carter gave them hope with his second goal in two games after he latched on to a misplaced clearance from Jonny Evans to fire home from 18 yards in the 72nd minute.
But the damage had already been done and it was a case of too little too late for Tony Mowbray's out-of-sorts side.
To add to their misery, left-back Paul Robinson was also dismissed in the 87th minute for bringing down substitute Liam Miller as Sunderland held on for a priceless win which ensured that Keane survived the curse of the Manager of the Month award having picked up the accolade for February on Thursday.
Sunderland have now won five of their last six games and are building up a head of steam at just the right time.
The victory moved them level on points with third-placed Albion who looked distinctly jaded following their FA Cup clash against Middlesbrough on Tuesday.
They never managed to hit the heights as 21-goal Diomansy Kamara and 14-goal Kevin Phillips struggled to make any kind of impact.
Any hopes Albion had of mounting a comeback after regrouping at half-time disappeared just after the re-start when David Connolly's shot was deflected for a corner.
John was left unmarked at the far post to head home Dean Whitehead's cross for his third goal since his arrival from Coventry City in January.
Yorke really ran the show for Sunderland in the first half and his goal was a just reward for the amount of work that he got through.
While Albion saw plenty of the ball themselves, they struggled to make any kind of headway against the imposing physical presence of Sunderland's central defenders, Nyron Nosworthy and Evans.
Former Sunderland marksman Phillips saw his header loop onto the top of the net and Jason Koumas fired wide before Albion's defence was torn apart in some style after 24 minutes.
Right-back Danny Simpson cut in from the wing and fed a short pass into the path of John.
The well-travelled striker then released the unmarked Yorke and the former Manchester United marksman drilled his low shot beyond Dean Kiely from 14 yards.