Mauricio Pochettino's men looked like enjoying a comfortable afternoon against the Argentine's former club having taken a two-goal lead in the first half through Dele Alli and Christian Eriksen.
However, Southampton improved as the match went on and made it a nervy second half when James Ward-Prowse netted in the 52nd minute to keep the White Hart Lane faithful on the edge of their seats.
Spurs came out of the blocks quickly, forcing Southampton goalkeeper Fraser Forster into a good save after three minutes, the Englishman standing up well to stop Heung-min Son flicking the ball past him.
It was not long before the home side made the breakthrough as Mousa Dembele rolled the ball into the path of Eriksen, the Dane cutting in from the right, knocking the ball out of his feet before arrowing a low drive into the bottom corner from long range.
Forster had to be sharp stopping former Saint Toby Alderweireld doubling Tottenham’s lead with a close range header before Manolo Gabbiadini went close to an equaliser for the visitors, the in-form Italian failing to squeeze the ball in at the near post.
Gabbiadini went off with a groin strain two minutes later and Southampton’s day only got worse when Steven Davis was adjudged to have felled Dele Alli in the box. The England midfielder dusted himself off to roll home the penalty for his 16th goal of the season.
Saints should have had their own spot kick before half-time when Ben Davies got away with a foul on Dusan Tadic inside the box.
Southampton got themselves back in it seven minutes after half-time when Spurs failed to cut out Ryan Bertrand’s cross, the ball bouncing all the way across the face of goal to James Ward-Prowse, who marked his England call-up by slamming his shot home.
Son missed the chance to respond immediately after Ward-Prowse’s goal, turning inside the box but slicing his shot wide.
A tight second half produced few opportunities for either side, Sofiane Boufal’s long-range strike as close as the Saints got to an equaliser.
Spurs hung on though to claim a 10th successive home win in the Premier League and strengthen their grip on second while Southampton stay 10th.