The hosts showed early sparkle before first-half goals from Gareth Bale – returning to haunt his former club – and Clint Dempsey put the visitors in control.
Jay Rodriguez responded after the break but it wasn’t enough to prevent the hosts suffering their seventh defeat of the season whilst Spurs are back in the top four.
Despite their early intent, Nigel Adkins’ men almost became architects of their own downfall when Maya Yoshida’s mistimed header fell to Aaron Lennon but the England winger fired wide.
It was Welsh international Bale, playing for the first time since the birth of his child, who soon made amends, planting a firm header beyond Artur Boruc following Tom Huddlestone’s cross (15).
The visitors sensed an opportunity to score a second and it came when Jermain Defoe beat Boruc, before Jose Fonte’s clearance allowed Dempsey to tap in.
The home side emerged after the break with renewed promise, lively forward Jason Puncheon leading the charge with a booming volley before Yoshida headed wide after Brad Friedel failed to handle Danny Fox’s delivery.
Already reinvigorated, the introduction of Emmanuel Mayuka breathed new life into Saints and they were rewarded on 66 minutes courtesy of Rodriguez.
Fonte was the architect, his cute back-heel from Adam Lallana’s corner falling to the former Burnley striker, who rifled the ball home from close range.