Having scored against the Baggies in the Premier League and the initial fourth round tie, Defoe bagged two more in the replay at the Lane including an absolute scorcher to put us ahead after a tricky start to the game.
The second half brace turned the tie on its head after West Brom had the better of the first half and took the England star's tally to 19 goals in all competitions this season.
As Defoe grabbed the headlines, Paul Robinson deserved equal billing after a series of fine saves in the first half.
Indeed, there would have been few complaints had we gone in trailing at the interval.
Thankfully, that wasn't the case as Robbo kept West Brom out and then Robbie Keane kept his cool in a four-minute wait to take a penalty to level just before half-time.
The first half boiled down to the two keepers with Robinson at his international best to keep West Brom at bay while Russell Hoult's only serious action ended with the penalty and him back in the changing room with a gashed eye, replaced by Tomasz Kuszczak.
Baggies started the better and deserved the lead via Kanu's header on 11 minutes after Campbell back-heeled for Gera to cross.
The visitors then came close twice in a minute with Robinson first denying Campbell one-on-one before clawing out namesake Robinson's curler.
We came more into the game and Clement did well to deny Keane a shooting chance from Kanoute's knock down but we needed Robinson at his best to keep it at 1-0 after 34 minutes.
Campbell played a one-two with Gera and was through in the right side of the box, hit his shot low and it was destined for the bottom corner before the slightest of touches took it wide.
Defoe smashed our best chance into Park Lane after 37 minutes but we were soon level. Kelly darted onto a ball over the top, got there before Hoult and as he flicked the ball over the keeper, Hoult's momentum took him out.
Replays showed his head actually connected with Kelly and a gash under the eye forced him off the field.
His replacement was Tomasz Kuszczak and, four minutes after the incident, Keane sent him the wrong way from the spot.
Martin Jol took off Keane at half-time, replacing him with Simon Davies and reverting to a 4-4-2 system.
The second half was a completely different story.
It took just four minutes for us to nudge ahead with a stunning strike from Defoe. Awarded a free-kick 20 yards out for handball, most were looking at a strike from Reto Ziegler but he instead rolled it into the path of Defoe just inside the box and the striker almost took the net off.
Five minutes later and Defoe struck again, making no mistake after fine work from Kanoute down the left flank.
Brown went flying in to head straight at Kuszczak after 57 minutes but there was then a lull in the action, a few substitutions and it wasn't until the last minute that either keeper was tested again, Robinson showing strong hands to parry away Clement's piledriver of a free-kick.
Davies almost capped the evening in injury time but forced the best out of Kuszczak but the fans were thinking about Forest in round five next Sunday a long time before that.
GUIDE TO THE ACTION
3mins: First shot, ambitious 30-yarder from Scimeca that flew into Paxton Road.
7mins: Decent move from West Brom, Kanu into Campbell, wide to Gera, he crossed low aiming for Wallwork who didn't quite get there.
11mins: GOAL. Campbell chased ball down in right channel, back-heeled to Gera whose cross was headed home by Kanu from 10 yards.
Spurs 0, West Brom 1
14mins: SAVE. Campbell onto flick, through on goal, side-foot attempt read by Robinson who saved to his left.
14mins: SAVE. Robinson at full stretch to claw out Robinson's curler with outside of left foot.
21mins: Couple of dangerous moments - Koumas free-kick from right caused problems, Kelly had to scramble out corner and Wallwork's 20-yarder well blocked.
23mins: Defoe beat offside trap, good control and laid back to Carrick whose low shot was blocked, Hoult prevented corner.
32mins: Clement fine tackle to deny Keane a shooting chance as he ran onto Kanoute's chest down.
34mins: SAVE. Robinson's best so far as West Brom cut us open, Campbell one-two with Gera, through on goal, right channel, low shot goalbound but for slightest touch from the keeper.
37mins: CHANCE. Kanoute did well to win possession from Koumas, pinpoint cross found Defoe 12 yards out, volleyed over.
38mins: Crossfield pass from Robinson picked out Gera who shot across goal from 20 yards.
40mins: PENALTY. Kelly onto ball over the top, beat Hoult to it who actually took him out with his head on the slide. Definite foul.
43mins: Hoult off in a daze replaced by Kuszczak.
44mins: GOAL. Keane sent Kuszczak wrong way from spot.
Spurs 1, West Brom 1
Half-time: Spurs 1, West Brom 1
Half-time: SUB. Davies for Keane.
49mins: GOAL. Clever free-kick routine, Ziegler laid ball square for Defoe to hammer home from 16 yards. Unstoppable.
Spurs 2, West Brom 1
54mins: GOAL. Kanoute did all the hard work down the left, beat Gaardsoe, crossed from byline for Defoe to drill home from 10 yards.
Spurs 3, West Brom 1
56mins: Koumas low shot from 20 yards gathered easily by Robinson.
57mins: CHANCE. Brown flying in to meet Davies cross but directed header straight at Kuszczak.
61mins: YELLOW. Campbell for late tackle on King.
61mins: SUB. Earnshaw for Defoe.
68mins: SUB. O'Connor for Scimeca.
79mins: PENALTY? Claims again as Defoe latched onto Carrick's fine pass but Kuszczak got enough on the ball.
81mins: Davies burst from midfield, almost got to it but still managed to charge down attempted clearance from Kuszczak, ball rebounded towards Kanoute but Robinson there to hack away.
87mins: Wallwork for foul.
89mins: SAVE. Robinson strong parry away to Clement's piledriver free-kick from 20 yards.
Injury time: SAVE. Quick break, Kanoute control and rolled into path of Davies who hit it well but was denied by Kuszczak tip over.
Full-time: Spurs 3, West Brom 1
Spurs (4-4-2): Robinson, Kelly, Gardner, King, Atouba; Ziegler, Carrick, Brown, Keane (Davies, 45); Kanoute, Defoe. Subs: Cerny, Mendes, Naybet, Edman.
West Brom: Hoult (Kuszczak, 43), Scimeca (O'Connor, 68), Robinson, Gaardsoe, Koumas, Gera, Albrechtsen, Clement, Campbell, Wallwork, Kanu (Earnshaw, 61). Subs: Purse, Horsfield.
Jermain Defoe took his tally to four goals in three games against West Brom this season to fire us into the fifth round of the FA Cup on Saturday evening.