The striker was at his lethal best in front of goal as we dominated from the first to the last minute against the Slovenian champions.
Two goals came from Gareth Bale assists with the winger at his unstoppable best down the left. Tom Carroll, who impressed in central midfield, created Defoe's other goal.
JD's hat-trick took him above legend Teddy Sheringham and into eighth in the club's all-time goalscoring list with 126 goals for us in 313 appearances.
The win moved us into second place in Group J, two points behind Lazio - who beat Panathinaikos 3-0 in Rome - and now two points ahead of Maribor. We travel to Lazio next on November 22.
Andre Villas-Boas made five changes from the starting line-up that faced Wigan on Saturday.
Most notable was Emmanuel Adebayor making his first start of the campaign after five substitute appearances, partnering Defoe up front.
Carroll came in for his second start this term with Michael Dawson back as captain, Hugo Lloris in goal and Kyle Naughton at left-back.
Brad Friedel, William Gallas, Steven Caulker, Sandro and Clint Dempsey made way.
It seemed incredible that we went in level at half-time after completely dominating the first half.
Bale glanced the first effort at goal from Huddlestone's corner, cleared off the line by Arghus, Defoe volleyed wide and then Bale pulled Huddlestone's raking free-kick out of the air and drove in a cross that just evaded Adebayor.
Defoe was then inches away from another Bale cross but rose well to meet Adebayor's centre on 20 minutes, only to head straight at Jasmin Handanovic in the Maribor goal.
The opener had to come and arrived on 22 minutes. It was no surprise that Bale was the provider and equally that Defoe was on the end of it - Bale whipped in a cross from the left and Defoe didn't break stride in guiding it into the corner.
Bale was relentless and soon zipped past his full-back Martin Milec again, this time shooting straight at Handanovic and he then crossed for Adebayor to head straight at the goalkeeper.
Lennon and Bale switched flanks and Lennon was straight at Milec, his cross found Kyle Walker straining every muscle but not quite enough to fashion a header at goal.
A second goal seemed inevitable - but no-one in the stadium expected it to be at the Paxton Road end.
Maribor carved out their first chance in the 39th minute when Lloris palmed out Tavares' cross and Goran Cvijanovic headed the loose ball onto the roof of the net.
Maribor kept up the pressure, Naughton was penned in on the left touchline and opted to go back to Lloris but Robert Beric was loitering and Lloris had nowhere go to. He tried to made a yard of space to clear but Beric got a foot in and the ball rolled agonisingly over the line.
The sight of Fabrice Muamba at half-time - back at the Lane for the first time since his cardiac arrest in March and subsequent, amazing, recovery - warmed the hearts of everyone in the stadium and the lads were soon back on top in the second half.
It took just four minutes to regain the lead as Carroll threaded a pass through to Defoe, who finished in style across Handanovic into the bottom corner.
Beric had another sight of goal, heading over from Agim Ibraimi's free-kick, but it was a brief respite for the visitors as Bale conjured up a pass for Adebayor, scooping the ball over the defensive line, only for the striker to volley wide from six yards.
Handanovic produced a sharp save to his left from Adebayor when the next chance arrived on 74 minutes and it was soon 3-1 with a trademark Spurs goal - Huddlestone sent Bale charging down the left and he delivered the inch-perfect cross on the run for Defoe to slot home his hat-trick and put the game beyond doubt.
It could have been more - Lennon had a clear sight of goal but tried in vain to find Adebayor and Dempsey, on for Defoe, who received a standing ovation, did well to turn away from two defenders but found Handanovic equal to his curler.
Spurs (4-4-2): Lloris; Walker, Dawson, Vertonghen, Naughton; Lennon (Falque, 90+1), Carroll, Huddlestone, Bale (Mason, 86); Adebayor, Defoe (Dempsey, 82). Unused subs: Cudicini, Gallas, Livermore, Sigurdsson.
NK Maribor (4-4-1-1): Handanovic; Milec, Arghus, Rajcevic, Mejac; Ibraimi, Mertelj (Dodlek, 89), Filipovic, Cvijanovic (Mezga, 69); Tavares (Komazec, 76); Beric. Unused subs: Pridigar, Vidovic, Potokar, Viler.
Goals: Spurs - Defoe (22, 49, 77). Maribor - Beric (40).
Yellow cards: Spurs - Bale (53), Carroll (75). NK Maribor - Mejac (38)
Referee: Mr A Munukka (Finland).