Seb Larsson's stoppage-time free-kick gave Sunderland a 2-1 victory over Blackburn Rovers and Stoke winger Matthew Etherington scored twice to sink 10-man Spurs at the Britannia Stadium in a match full of controversy.
Third-placed Spurs, who had won six successive league games and not lost one since August, fell behind in the 13th minute when striker Peter Crouch set up fellow former Tottenham player Etherington for a powerful finish.
Crouch appeared to handle the ball in the build-up but Spurs had nothing to complain about when Jon Walters flicked on Ryan Shotton's long throw and Etherington scooped in at the far post two minutes before the break.
The visitors struck back in the 62nd minute when Stoke midfielder Glenn Whelan tripped Luka Modric in the area and Emmanuel Adebayor converted the penalty, sending goalkeeper Thomas Sorensen the wrong way.
The lively Modric could have levelled with a long-range shot that Sorensen tipped behind and Adebayor put the ball in the net in the 75th minute but was ruled offside when television replays showed he had not been.
Just before that, Younes Kaboul's goal-bound shot was blocked on the line by Stoke defender Ryan Shawcross's arm. Kaboul was booked for his protests and eight minutes from time was sent off for a second yellow following a foul on Walters.
Spurs manager Harry Redknapp was not happy with referee Chris Foy.
"A couple of the decisions today were amazing," he told Sky Sports.
"I just watched the video replays - Adebayor was a yard and a half, maybe two yards, onside. They've handled the ball on the line, it's blatant handball, Younes Kaboul got a yellow card for saying to the referee 'referee, he handballed it'.
"I wouldn't want to comment about what I thought about the referee's performance today. I never come on TV and complain about referees... but it was disappointing today."
The result kept Tottenham in third place, five points behind Manchester United with a game in hand. Leaders Manchester City, who are two points clear, travel to fifth-placed Chelsea on Monday. Stoke moved up to eighth.
The rousing reception given to new manager O'Neill at the Stadium of Light was temporarily forgotten when Blackburn went in front in the 17th minute with a Simon Vukcevic header.
The hosts, who dominated possession against their defensive visitors, were denied by superb saves from Blackburn goalkeeper Paul Robinson before David Vaughan's 84th-minute equaliser from 25 metres out started the late turnaround.
Two minutes into stoppage-time, Sunderland were awarded a free-kick 20 metres out and Larsson stepped up to curl in a stunning effort that sent the home fans into noisy celebrations as O'Neill jumped up and down on the touchline.
"We have got some points on the board, which is vital for our confidence and vital for the crowd," O'Neill told Sky Sports.
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