Defoe's opening goal was cancelled out by an equaliser from the Slovenian side as Kyle Naughton and Hugo Lloris got in a tangle before the England striker struck twice more in the second half.
Spurs began in impressive fashion, with Gareth Bale causing problems down the left flank from the outset.
The Wales international struggled to find a telling cross until midway through the opening half though, when he picked out Defoe for the opening goal.
Bale whipped the ball into the area and Defoe opened up his body to direct a side-footed volley past Maribor keeper Jasmin Handanovic and into the corner of the net (22).
Emmanuel Adebayor tried to extend the lead but he could only direct a weak header straight at Handanovic as Andre Villas-Boas' side failed to turn possession into goalscoring opportunities.
Instead it was Maribor who grew in confidence as the half progressed, with Goran Cvijanovic nodding over after Tottenham goalkeeper Lloris could only palm a low cross from Marcos Tavares in his direction.
If that was a warning then Spurs failed to heed it and their Slovenian opponents were level five minutes from half-time in farcical circumstances.
Naughton played an inadvisable back-pass to Lloris and as the Frenchman tried to clear, Robert Beric intercepted and slotted the ball into an empty net.
But Tottenham regrouped at the break and regained the lead four minutes after the restart, Defoe on target again as he latched onto a first-time ball through from Tom Carroll to fire a low shot into the bottom corner of the goal.
That moved the England international onto 14 goals in European club competition for Spurs to move him into second place behind Martin Peters in the club's list of highest scorers.
Adebayor almost added another but he volleyed wide as he failed to properly control a ball from Bale, with Maribor defender Arghus Soares then lucky to stay on the field after appearing to foul Defoe just outside the area.
Handanovic made a smart save to deny Adebayor as Spurs dominated but he could do nothing to prevent Defoe securing his treble, a flowing move ending with the striker getting ahead of his marker to slot home another pinpoint Bale cross on 77 as the home side wrapped up the win.