Christian Eriksen pulled a goal back for Spurs moments later before getting them back on level terms at the start of the second half.
The match looked to be heading for a draw until substitute Gylfi Sigurdsson smashed the ball home deep in stoppage time to give Spurs the points.
Here, Sports Mole takes a closer look at the action between the two teams at White Hart Lane.
On target: 6
On target: 4
Was the result fair?
It is hard to say that Spurs deserved all of the points purely because Southampton played their part in an entertaining encounter. Saints boss Mauricio Pochettino is sure to feel aggrieved that his side did not come away with a share of the spoils having worked so hard for much of the 90 minutes.
Tottenham were poor during the first half as they failed to cope with Southampton's inventive and incisive attacking play. The hosts committed far too many errors and struggled to get to grips with the fluid tactics of their opponents. That all changed after the break, though, when they levelled the match through Eriksen. From that point onwards, Tim Sherwood's side took the game by the scruff of the neck, showing plenty of hunger and desire to come away with the three points. This result could be a huge one come the end of the season.
The Saints were excellent during the opening 45 minutes, cutting Spurs apart time and again with some confident passing and movement from their forward players. Had it not been for some disappointing finishing, then they could have had a couple of more goals for their efforts. Their downfall came at the start of the second half when they conceded an equaliser almost instantly, and from there it was a case of defending deep and trying to keep Spurs out. It looked like they had succeeded in doing that with an organised display at the back before Sigurdsson's late winner.
Sports Mole's man of the match
Christian Eriksen: Not only did the Dane score two vital goals for Spurs, but he also provided them with a dynamic presence going forward for much of the match. He was their shining light during a lacklustre first half before maintaining that level after the break to help them pick up three important points.
Kayle Naughton was at fault for both of Southampton's goals, but his error for their first was the worst. The full-back allowed Artur Boruc's long hoof upfield to bounce over his head which saw Jay Rodriguez sneak in and confidently finish past Hugo Lloris.
Anthony Taylor gave a competent display out in the middle as the two teams played out an exciting encounter. Southampton may feel that there was foul on Dejan Lovren by Roberto Soldado before Spurs' second goal, but Taylor did the right thing by letting play continue.
Spurs: Tottenham continue their Premier League campaign next Sunday when they face Liverpool at Anfield.
Southampton: The Saints are back in action on Saturday at home to Newcastle United in the Premier League.