Danny Ings opened the scoring in the 30th minute from James Ward-Prowse's corner, while Spurs scored twice in the second half via Gareth Bale and Son Heung-min.
While Spurs players struggled to find rhythm throughout the game, they cannot be completely blamed, considering the series of events that have unfolded at the club in the last few days.
Despite all the chaos involving the European Super League and the sacking of Jose Mourinho, they ensured that Ryan Mason, a former Spurs midfielder, had a winning start to his managerial career at the club.
Here, we take a look at the five talking points as Tottenham Hotspur move into sixth place in the Premier League standings.
#5 Gareth Bale relishing his second spell with Tottenham Hotspur
Gareth Bale stepped up when Tottenham Hotspur needed him the most on Wednesday.
In the absence of Harry Kane, the goalscoring responsibility largely fell on Son Heung-Min. While the South Korean star managed to score the winning goal, it was Bale's equalizer that proved to be the turning point in the game.
The Welshman was in the right place at the right time, as the ball fell to him after Lucas Moura's shot was blocked by Salisu in the box.
The winger took a touch to bring the ball to his preferred left foot and curled an exquisite shot into the top left corner of the goal.
Bale is certainly enjoying his second spell at Tottenham Hotspur and has been involved in 11 goals in his last 11 starts for the club.
#4 Southampton's first-half brilliance faded away after the break
Southampton were in the driving seat for the first 45 minutes of the game. Having capitalized on Tottenham Hotspur's lackluster defending, they managed to score from a routine corner.
The goalscorer was none other than Danny Ings, who now has 10 goals to his name this season. His goal gave the Saints a much-needed boost. However, when he was taken off in the second half, the visitors just couldn't find their groove.
Ralph Hasenhüttl will now need to rework his strategy, given that Ings is once again out with an injury.