Ange Postecoglou's side had established a two-goal lead after Brennan Johnson and James Maddison scored in the first half.
However, Tottenham fell apart in the second period and Brighton took full advantage as they won the game in dramatic fashion.
Yankuba Minteh, Georginio Rutter and Danny Welbeck all scored as Brighton took all three points.
Tottenham boss Ange Postecoglou was left hugely frustrated with how his team collapsed.
As reported by Opta, the game against Brighton was the tenth time in which Tottenham have lost a Premier League game in which they led by two or more goals.
Tottenham are the first team to reach double figures for this statistic, with this scenario having occurred at least three more times than for any other club in Premier League history.
The defeat to Brighton wasn't the only 3-2 loss that Tottenham suffered on Sunday.
Tottenham Women side lost 3-2 at home to Liverpool, which included conceding a penalty in stoppage time.
Cornelia Kapocs had put Liverpool in front before an own goal from Taylor Hinds saw Tottenham equalise.
Marie-Therese Hobinger scored a brace for Liverpool, which included a late penalty
Liverpool regained the lead courtesy of Marie-Therese Hobinger, with Clare Hunt then levelling for Tottenham.
Liverpool took all three points, with Hobinger scoring a late penalty.