The result lifts West Ham above Tottenham on the Premier League table and into the top four.
Spurs failed to create opportunities of note in the second half and Nuno Espirito Santo said defeat was tough to take, although he thought Tottenham were the better team.
"We're disappointed like everyone, like our fans. It's always tough to lose a match like this," Nuno said.
Antonio -- who had trials at Tottenham when he was 14 -- had most of the chances, troubling the Spurs defence on more than one occasion. Cristian Romero had a particularly difficult match with the 31-year-old, often left second best on their one-on-ones.
It was 72 minute into the game, though, before Antonio found the breakthrough from a corner. Aaron Cresswell sent the ball into the box and Antonio flicked it into the net at the near post.
"The ball came my way and obviously being the poacher I am, I stick my foot out. I was surprised it went in because I kind of got my foot there to get in front of him," Antonio told Sky Sports after his sixth goal against Spurs.
"[Whether] it's this stadium or their stadium, I just like scoring against them... I have the No. 9 shirt and that's what I need to do."
Information from Reuters contributed to this report.