The striker opened the scoring in spectacular fashion just before the break to hand us that all-important lead and then tapped home his second and our third after Aaron Lennon presented him with an open goal on 64 minutes.
In-between, Gareth Bale applied the finish that Clint Dempsey's clever assist deserved on 58 minutes.
The margin of victory could have been much more as we dominated - 25 efforts at goal and 65 per cent possession tells the story - but the Hammers struck last with a consolation goal from Andy Carroll to make it 3-1 eight minutes from time.
Even then, Defoe had the chance to complete a hat-trick against his former club but Jussi Jaaskelainen blocked with his feet.
Andre Villas-Boas made four changes to the team that started at Lazio on Thursday night - Michael Dawson for Kyle Naughton, Tom Huddlestone for Tom Carroll, Lennon for Gylfi
Sigurdsson and Defoe for Emmanuel Adebayor.
Dawson captained the team in what was his first start in the Premier League this season with Jan Vertonghen switching again to left-back.
We tore into the Hammers from the first whistle, underlined by eight efforts at goal inside the first 25 minutes.
Defoe blazed wide early and curled straight at Jaaskelainen and then Bale let rip from 25 yards, the ball crashed off the underside crossbar and bounced just in front of the goal-line. Dempsey was first on the scene but couldn't get enough power on his header to beat Jaaskelainen, who grabbed the ball on his line.
The US striker tried his luck again a minute later, a curler from the edge of the box and this time Jaaskelainen saved down to his left.
Huddlestone, twice and Dempsey fired wide but West Ham started to find their feet and Dawson did well to intercept Kevin Nolan's pass that would have sent Matt Jarvis clean through - Jarvis off the bench early to replace Modibo Maiga. Dawson and Steven Caulker then combined to block Nolan's shot.
The first half performance deserved a goal - and Defoe delivered in style in the 44th minute.
Picking up the ball on the right touchline, he controlled, turned inside Winston Reid and headed for goal. He cut back onto his right foot, slipped past Noble and then unleashed an unstoppable shot past Jaaskelainen from 22 yards.
The start of the second half matched the first in terms of tempo and intent and the points were all-but in the bag by 65 minutes.
Bale hit a dipping free-kick just wide, George McCartney slid in to block from Defoe and after Hugo Lloris made his first save of note to turn away Jarvis's low effort, Sandro released Defoe but this time James Tomkins did enough to take the sting out of the shot.
The teams traded a couple of chances - Jaaskelainen on his toes to palm out Bale's fizzer, Lloris equally alert to grab Nolan's low cross intended for Jarvis - before we hit a purple patch either side of the hour.
It started with Dempsey rifling a shot that cannoned back off the post but he was soon back on the ball to set-up the all-important second goal. This time, he drove forward from half-way and reached the edge of the box, where he had the vision to dink a pass to Bale, who managed to angle his shot in off the post for 2-0, 58 minutes on the clock.
Dempsey was also involved six minutes later as Defoe doubled-up for 3-0. This goal owed much to Sandro winning a 50-50 centrally and then Dempsey was alert to flick the ball to Lennon, who sped through on goal. Dempsey and Defoe both followed the winger into the penalty box and Lennon did the sensible, unselfish thing, squaring for Defoe to tap into an empty net.
Substitute Matt Taylor fired just wide for West Ham but we continued to press with some lovely play in and around the box - Bale was inches away from touching home Dempsey's cross and Walker lashed into the side-netting.
West Ham broke through eight minutes from time when Carroll looped his header into the corner from Joey O'Brien's cross.
Jaaskelainen produced a double save to deny Defoe a hat-trick and keep out Bale's 20-yard curler destined for the bottom corner and, as we ticked into five minutes of added time, West Ham might have made it an uncomfortable final few minutes but Lloris was there to make a flying save from Reid's close-range header.
Spurs (4-2-3-1): Lloris; Walker, Caulker, Dawson, Vertonghen; Huddlestone, Sandro (Livermore, 86); Lennon (Dembele, 79), Dempsey, Bale; Defoe (Sigurdsson, 90+4). Unused subs: Friedel, Gallas, Naughton, Carroll.
West Ham (4-2-3-1): Jaaskelainen; O'Brien, Tomkins, Reid, McCartney; Diame, Noble; O'Neil
(Taylor, 55), Nolan (Cole, 69), Maiga (Jarvis, 31); Carroll. Unused subs: Spiegel, Collins, Demel, Moncur.
Goals: Spurs - Defoe (44, 64), Bale (58). West Ham - Carroll (82).
Yellow cards: Spurs - Defoe (33). West Ham - O'Brien (7), Noble (29).
Referee: Mr A Marriner.