Sam Allardyce's men won twice at White Hart Lane earlier this season, in the Premier League and League Cup, and were dominant for large spells on this occasion against a Spurs side reduced to 10 men during the first half.
After a reasonably open start to proceedings, Younes Kaboul was sent off after 25 minutes for bringing down Stewart Downing as the winger bore down on goal.
Things got worse for Tim Sherwood when an Andy Carroll header deflected in off Harry Kane just two minutes later and, on the stroke of half-time, Downing scored his first goal for West Ham with a free-kick from the edge of the area.
The result dents sixth-placed Spurs' hopes of securing UEFA Europa League football for next season.
West Ham, meanwhile, are guaranteed another campaign in the top flight, with a first win in five providing a welcome boost to manager Allardyce, who has been the subject of regular criticism from his own fans of late.
Carroll caused the visiting defence problems early on but it was Emmanuel Adebayor at the other end who should have opened the scoring.
After Christian Eriksen cleverly played him in, the Spurs forward side-footed a tame effort straight at Adrian.
Guy Demel almost profited from Carroll's aerial presence to strike the crossbar with a mis-hit strike on the turn.
Spurs then appeared to have little reason for complaint as Kaboul bundled over Downing just outside the area and was sent off.
Carroll's free-kick forced Hugo Lloris to make a smart stop and the England international helped open the scoring from the resulting corner, with his header clipping Kane and looping over Tottenham's goalkeeper to cap off a woeful few minutes for the visitors.
West Ham piled on the pressure for the remainder of the half and another foul on the edge of the box led to their second goal.
Mark Noble was brought down by Michael Dawson before Downing converted the free-kick, with Lloris likely to be disappointed with the lack of protection offered by his wall.
Mohamed Diame found the target with an overhead kick shortly after the break, while Nolan was also thwarted by a busy Lloris.
The introduction of Roberto Soldado and Sandro had little effect as Tottenham struggled to find a way back into the game, with the former spurning two half-chances.
Adrian made a fine save to deny Danny Rose in injury time, but West Ham were all but assured of victory by then and Sherwood's men could now find themselves pipped to the final Europa League place by Manchester United.
