Andre Villas-Boas' team raced into the lead in the first half but had to survive a late Saints onslaught in order to collect three points at St Mary's on Sunday afternoon
The Wales international, who left Saints in 2007, powered home a 15th minute header to open the scoring, before Clint Dempsey added a second before half-time with Spurs dominant in all areas against the insipid hosts.
And although Jay Rodriguez set up an enthralling final 20 minutes by smashing home from a tight angle, Andre Villas Boas' side closed out the win to rise 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 left-back Danny Fox coming in for Guly Do Prado and Jos Hooiveld.
For Spurs, Bale returned to his former club for the first time since his departure, replacing Gylfi Sigurdsson in Villas-Boas' midfield.
Spurs had been on a tremendous run of form until their 4-2 defeat at the hands of Chelsea and they 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 their undoing when Tom Huddlestone was afforded the space to pick out Bale with a sumptuous delivery. The winger powered a downward header past Artur Boruc and into the far corner of the net.
Defoe has been in sparkling form this season, but his radar seemed to be off on the south coast after he collected another Walker pull-back on the edge of the area only to smash an uncontrolled effort well over. The England striker was involved, however, when Tottenham deservedly doubled their lead six minutes before the break.
Aaron Lennon slipped Defoe in behind a static Saints defence 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 that it hit the stadium scoreboard after more incisive build-up play from Spurs.
Southampton started to edge their way back into the game, however, and Maya Yoshida should have done better than to head wide after Brad Friedel had missed a cross.
From the subsequent corner though, Rodriguez smashed home from a difficult angle to halve the deficit and set up a pulsating final twenty minutes.
The former Burnley striker would have been disappointed not to have grabbed an equaliser moments later, driving a left-footed effort wide after the ball had fallen to him following more hesitancy in the Spurs defence.
The Saints onslaught continued as Lambert's close-range effort was well-blocked by William Gallas, with the St Mary's crowd becoming more vociferous by the minute.
And despite a further late surge, Spurs rode out the storm to propel themselves back into fourth, while Southampton will be left to rue missed opportunities as they continue to languish in the bottom three.