The striker was in electric form and delivered right on time as we ran out 3-1 winners in the fifth round replay at White Hart Lane.
Defoe lashed home with his left foot from 20 yards to level at 1-1 after Stevenage took an early lead from the penalty spot.
He was there again to make the tie safe with another clinical finish to make it 3-1 in the 74th minute.
That made it 15 for the season in all competitions and 116 for the club - just one goal behind Les Bennett and a place in our all-time top 10 goalscorers.
In-between Defoe's goals, Emmanuel Adebayor slotted home a penalty after Gareth Bale was fouled by Mark Roberts to hand us the lead 10 minutes into the second half.
The victory set-up a quarter-final against Bolton at the Lane on Saturday, March 17, kick-off 5.30pm.
Harry Redknapp made nine changes to the team that lost at home to United on Sunday.
Notable returns included Bale after illness, Rafa van der Vaart after injury and Scott Parker after suspension.
Michael Dawson lined-up with Ryan Nelsen, on his full home debut - the same central defensive pairing that played in the initial tie at Stevenage - and they were joined by Carlo Cudicini, Danny Rose, Niko Kranjcar and Defoe.
The start was nothing less than disastrous as Stevenage went 1-0 up and we then lost Dawson to injury with less than 10 minutes on the clock.
Nelsen fouled Joel Byrom in the box with three minutes gone and Byrom planted home his spot-kick.
Dawson then went up for a header, was nudged in the air by Chris Beardsley and landed awkwardly. He held his right leg for a while, made one attempt to get up but was eventually stretchered off.
Goalmouth action was at a premium as we slowly got back into the game, although the next chance of note went to the visitors as Michael Bostwick looped a header over from Byrom's free-kick.
The equaliser arrived on 26 minutes and it was typical Defoe.
Bale spotted his run and dropped the ball into his path from 50 yards and the striker did the rest, working a yard of space and crashing a left-foot drive past Chris Day from 20 yards.
Day did well to block at close-quarters from Defoe but we were then hit by another injury as Lennon trudged off with 38 minutes on the clock. The half ended with Bostwick dragging well wide from 22 yards.
We started the second half well and Defoe had the ball in the back of the net inside three minutes, only to be ruled offside.
Cudicini was then forced into a point-blank save to deny Mark Roberts after a scramble from a corner.
Roberts was involved in the action again a minute later - but not how he would have wanted.
Bale looked to cross from the right byline, Roberts threw himself in and referee Mr Oliver pointed to the penalty spot. Adebayor made no mistake.
Bale then dipped an effort onto the crossbar from 30 yards, Adebayor's header was deflected onto the roof of the net and Kranjcar fired just wide from the edge of the box.
Stevenage came close to levelling on 65 minutes when Scott Laird rose to power Byrom's corner onto the underside of the crossbar and out to safety.
We needed the third goal to put the game to bed and Defoe delivered again on 74 minutes.
It came after quick thinking from Bale, who found Defoe's run in behind with a long throw. There was still plenty to do but 'JD' was up to the task, turning onto his right foot and drilling across Day for 3-1.
The game was open in the final 10 minutes as Adebayor flashed a volley over, Cudicini saved well from Craig Reid and then Defoe inexplicably missed his kick in front of goal from Bale's cutback.
Spurs (4-4-2): Cudicini; Kaboul, Dawson (Walker, 8), Nelsen, Rose; Lennon (Adebayor, 38), Kranjcar (Livermore, 81), Parker, Bale; Van der Vaart, Defoe. Unsed subs: Friedel, Gallas, Rose, Giovani, Modric.
Stevenage (4-1-4-1): Day; Henry, Ashton, Roberts, Charles (Myrie-Williams, 62); Bostwick; Wilson, Byrom, Shroot, Laird; Beardsley (Reid, 62). Unused subs: Julian, Edwards, Long, May, Winn.
Goals: Spurs - Defoe (26, 74), Adebayor (penalty, 55); Stevenage - Byrom (penalty, 4).
Referee: Mr M Oliver.