The Welshman's third goal of the season and a Clint Dempsey strike looked to have set Villas Boas's side en-route to an easy win, but it had to survive a late Saints onslaught.
The Welshman who left Saints in 2007 powered home a 15th minute header to open the scoring, before Clint Dempsey added a second before halftime with Spurs dominant in all areas against an insipid Southampton outfit.
Although Jay Rodriguez set up an enthralling final 20 minutes having smashed home from a tight angle, Andre Villas Boas’s side closed out the win to take it back into the top four.
Southampton boss Nigel Adkins made two changes to the side hammered by West Ham last week, with striker Rickie Lambert and midfielder Daniel Fox coming in for Guly Do Prado and Jos Hooiveld.
For Spurs, Bale returned to his former club for the first time since his 2007 departure, replacing Gylfi Sigurdsson in Andre Villas-Boas’s midfield.
Spurs have been on a tremendous run of form of late and started in a sprightly manner, fashioning the game’s first clear opening after only 13 minutes.
Having started to exert their authority in midfield, a lovely interchange of passes sent Kyle Walker free down the right flank but his pull back was slammed wide by Defoe from six yards.
Southampton failed to heed the early warning signs. Failure to pressure the ball proved the club's undoing when Tom Huddlestone was afforded the space to pick out Bale with a sumptuous delivery and the Welshman powered a downward header past Boruc and into the far corner of the net.
Defoe has been in sparkling form this season, but his radar seemed to be out of range on the south coast after he collected another Walker pull back on the edge of the area, before smashing an uncontrolled effort well over.
But the England striker was involved when Tottenham deservedly doubled the lead, six minutes before the break.
Aaron Lennon slipped Defoe in behind a static Saints defense and although his shot was valiantly cleared off the line by Jose Fonte, Dempsey was on hand to smash in the rebound from three yards.
The second half started in a similar vein, with Defoe managing to sky a first-time shot so high it hit the St Mary’s scoreboard after more incisive build-up play from Spurs.
Despite further Spurs dominance, Southampton started to edge back into the game and Maye Yoshida should have done better than to head wide after Brad Friedel had missed a cross.
From the resulting corner though, Rodriguez smashed home from an angle to cut the deficit and set up a pulsating final 20 minutes.
The former Burnley striker would have been disappointed not to have grabbed an equalizer moments later, driving a left-footed effort wide after the ball had fallen to him following more hesitancy in the Spurs defense.
The Saints onslaught continued as Lambert’s close-range effort was well blocked behind by William Gallas, with the St Mary’s crowd becoming more vociferous by the minute.
Despite another late surge, Spurs rode out the storm to propel themselves back into fourth, while Southampton will be left to rue missed opportunities as it continues to languish in the bottom three.
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