Liverpool put up a brave fight before Joel Matip's own-goal deep into stoppage time handed Tottenham a 2-1 win on Saturday.
Liverpool looked set to hold on for a draw before Matip turned Pedro Porro's low cross into his own net in the sixth minute of added-on time.
The Reds had their backs to the wall after Curtis Jones was sent off in the 26th minute for a reckless challenge on Yves Bissouma and had to play the last 20 minutes, plus stoppage time, with nine men after substitute Diogo Jota picked up two yellow cards in quick succession.
Ange Postecoglou's team ended Liverpool's unbeaten start to the Premier League season and extended their own in to a pulsating clash in north London.
Jones was dismissed in the first half before Tottenham took the lead through Son Heung-min's opener.
Cody Gakpo equalised just before half-time but Liverpool were reduced to nine when Jota saw red after the interval.
It seemed Liverpool would hold out against the odds until Matip diverted Porro's cross into his own net with just seconds left.
After a dismal run of one win in their previous 23 meetings with Liverpool in all competitions, Tottenham could finally savour a win against the Anfield outfit.
It was Tottenham's first win against Liverpool since 2017 when the north Londoners were using Wembley as their temporary home.
Postecoglou's men moved above Liverpool into second place, just one point behind Manchester City after the treble winners' surprise loss at Wolves earlier on Saturday.
Liverpool, beaten for the first time in nine games in all competitions, are one point behind Tottenham in fourth place.
Despite the defeat, Liverpool boss Jurgen Klopp said he was proud of his team.
"I was never more proud of the team than today. I never saw a game like this with the most unfair circumstances, crazy decisions," he told Sky Sports.
"We scored an own goal, that is really tough to take but I am really proud. The first red card, Curtis steps on the ball and goes over. Not a bad tackle.
"It looks different in slow motion. He steps full throttle on the ball and goes over the ball. That is unlucky."