Defoe's treble was all about his poacher's instincts in front of goal with fine finishing after seven, 26 and 60 minutes.
Fredi Kanoute and Robbie Keane chipped in with a goal each as we led 3-0 at the break after a wonderful first half display.
Hearts would have skipped a beat (with FA Cup 4-3's to Manchester City in mind) when Peter Crouch replied a minute into the second half for 3-1 but Defoe's hat-trick quickly calmed nerves and we dominated the rest of the game.
Top scorer Defoe came back into the starting line-up after suspension for Robbie Keane, who was on the bench. Reto Ziegler also returned after injury with Anthony Gardner in for injured Noureddine Naybet.
The first half was as good a performance as we've seen all season with goals, saves and plenty of chances created.
Defoe's opener after seven minutes owed a lot to Michael Carrick who helped end a dangerous Southampton attack, took the ball out of our box and swept a lovely pass up the right touchline to Kanoute. His control took him away from Danny Higginbotham and down to the byline where he waited and waited for Defoe to find a yard, fed in the perfect pass and Defoe did the rest.
Crouch flicked wide and actually looked to be combining well with Kevin Phillips but the play was concentrated at the other end as we dictated possession, Carrick at the heart of it.
The midfielder poked a shot at Antti Niemi and soon hit Kanoute from distance, he controlled and fed Defoe who flicked the ball over Darren Kenton before forcing Niemi into a fine save.
It was soon 2-0 though thanks to a slice of luck as Kanoute controlled Carrick's pass and turned but as he looked for a pass, Paul Telfer managed to get a foot in - only for his intervention to act at a through ball to the alert Defoe who finished in style.
Ledley King and Rohan Ricketts tried their luck and Niemi spectacularly saved from Kanoute after another Carrick pass after 38 minutes.
Telfer fired just wide and Noe Pamarot should have done better from Thimothee Atouba's fine first-time cross from the left but the third wasn't far away, Carrick again involved, this time lofting a pass to Kanoute over a Saints defence appealing for an offside flag that didn't come and Kanoute did the rest.
Paul Robinson still had to make a crucial save just before the break as Crouch got on the end of David Prutton's cross but it wass a happy White Hart Lane at the half-time whistle.
Hearts would have skipped a beat when Crouch jumped highest to head home a lifeline for the Saints just a minute into the second half as memories came flooding back of last season's 3-0 up at half-time, 4-3 loss in the FA Cup to Manchester City - thankfully, any doubts were quickly erased by Defoe's hat-trick goal 14 minutes later.
It was typical poacher's stuff as Lundekvam sliced a clearance, Brown won a key 50-50 on the edge of the area with Kenton, his volley was saved by Niemi but Defoe was there to bury the rebound.
That knocked the stuffing out of any potential Saints revival and Defoe soon went close again and substitute Pedro Mendes fired just wide.
Time was running out when Keane - also just off the bench - slotted a delightful fifth with Defoe cheekily lobbing the ball over the defensive line and the Irish striker doing the rest.
GUIDE TO THE ACTION
2mins: Defoe did well to hold off Higginbotham and drive in low cross, Niemi out to collect.
4mins: Long throw from Dodd flicked into six-yard box by Crouch, Robinson out quickly to gather.
7mins: GOAL. Great defending from Carrick, took ball away from danger then 40-yard pass up right touchline set up counter, Kanoute took ball to byline, waited, picked out Defoe to bury from 10 yards.
Spurs 1, Southampton 0
14mins: Poor back header from Higginbotham pounced on by Defoe, right side of box, attempted cutback to Ricketts slid out by Kenton.
15mins: Lively-looking Phillips onto Crouch knockdown, King there to deflect shot over.
15mins: From Svensson's corner, Crouch flicked header from near post area across goal and wide.
18mins: Decent possesion involving Carrick, Atouba and Ziegler ended with Carrick beating Lundekvam on edgfe of box but early toe-poke not enough power to trouble Niemi.
25mins: SAVE. All started with Kanoute typical chest control, laid in Defoe who flicked ball over Kenton, shot saved well low to his right by Niemi.
26mins: GOAL. Ziegler played ball into Kanoute, controlled and looked up only for Telfer's tackle to prod the ball through to Defoe, clean through, rolled ball home past Niemi.
Spurs 2, Southampton 0
28mins: King beat Niemi to punch from Carrick's corner but header flew over.
33mins: Phillips decent free-kick from 25 yards seen all the way by Robinson, who took easily.
37mins: Good build-up again before Ricketts lashed one over from 25 yards.
38mins: SAVE. Niemi spectacular full-length palm away as Kanoute aimed for top corner after Carrick sent him through.
39mins: CLOSE. Telfer let fly from 30 yards and screamed just wide with Robinson at full stretch.
40mins: Defoe didn't really get hold of 20-yarder, saved by Niemi.
41mins: YELLOW. Lundekvam for trip on Kanoute.
42mins: MISS. Great cross from Atouba but Pamarot, already up for free-kick, couldn't keep header on target from six yards.
43mins: GOAL. Carrick on ball, cut onto right foot, released Kanoute, clear on goal as Saints appealed for offside, side-footed into corner.
Spurs 3, Southampton 0
44mins: Prutton break down left, cutback for Crouch, eight yards out, good connection but Robinson equal to it low to his left.
Half-time: Spurs 3, Southampton 0
Half-time: SUB. Jakobsson for Nilsson.
46mins: GOAL. Prutton slid in cross that King sliced into the air, Robinson half-came, Crouch headed home from six yards.
Spurs 3, Southampton 1
50mins: YELLOW. Prutton for foul on Defoe.
51mins: Free-kick half-cleared, Brown control and volley straight at Niemi.
53mins: Kanoute won ball in midfield, carried past Dodd, cutback almost resulted in own goal.
54mins: SUB. Folly for injured Dodd.
60mins: GOAL. Defoe hat-trick. Lundekvam sliced clearance, Brown won key 50-50 against Kenton on edge of the area, volley saved by Niemi but Defoe there to mop up rebound.
Spurs 4, Southampton 1
65mins: SUB. Mendes for Ricketts.
74mins: Kanoute lobbed ball into Defoe, in on goal but Jakobsson to beat, twisted and turned but slid shot wide.
77mins: SAVE. Atouba mistake pounced on by Phillips, shot across goal from tight angle but ball stuck to Robinson low to his right.
81mins: CLOSE. Good build up with Mendes and Defoe, Kanoute laid ball back for Mendes to shoot just wide.
82mins: SUB. Keane for Ziegler.
87mins: GOAL. Defoe cheeky lob pass over the defensive line to Keane, superb control and finish.
Spurs 5, Southampton 1
88mins: Phillips blasted over from close range.
Injury time: Kanoute tricks, beat Jakobsson, drive into side-netting.
Full-time: Spurs 5, Southampton 1
Line-ups: Spurs (4-4-2): Robinson; Pamarot, Gardner, King, Atouba; Ricketts, Carrick, Brown, Ziegler (Keane, 82); Kanoute, Defoe. Subs: Redknapp, Davenport, Fulop.
Southampton: Niemi, Dodd (Folly, 54), Lundekvam, Phillips, A Svensson, Crouch, Higginbotham, Prutton, Kenton, Telfer, Nilsson (Jakobsson, 45). Subs: Smith, Beattie, Fernandes, Folly.
Referee: Philip Dowd.
Jermain Defoe helped deliver the perfect Christmas present at the Lane - his first hat-trick for us contributing to our biggest win of the season, four wins on the trot in the Barclays Premiership and seventh place on Saturday night.