Boss Mauricio Pochettino said it would take time to find unity in his squad after a turbulent summer where several players either wanted to leave or thought they were leaving, but they showed promising signs in a rearguard effort.
But Harry Kane came to the rescue as he scored a fine team goal, his fifth in the Premier League, to hand Spurs the three points that will go a long way to lifting the gloom at the club.
It was their third win of the season and Pochettino will hope that they can move forward ahead of Tuesday's Champions League clash with Bayern Munich.
Southampton enjoyed a spell of pressure early in the second half, but they did not really threaten an equaliser and slipped to a third defeat of the season.
Just once Spurs would like to do things the easy way and a straightforward afternoon looked a possibility after they enjoyed a promising opening 30 minutes.
After Lloris had thwarted early danger from Pierre-Emile Hojbjerg, with a smart stretching save, the home side – and specifically Ndombele – came to life.
The Frenchman has stuttered in his start to football in England, but showed why Spurs broke their transfer record on him.
He carried the ball, beating players, put some dangerous balls into the box and provided a goalscoring threat.
After seeing one goalbound effort deflected, he was rewarded with the opener in the 24th minute.
Any hopes of kicking on from there were abruptly ended in the space of four minutes as Aurier picked up two yellow cards for brainless fouls and was sent off in the 31st minute.
The last thing Spurs needed to do was give Southampton a helping hand, but that is what happened after an unforgivable piece of play from Lloris.
The Frenchman has a reputation for being a liability in possession – not something you want from a goalkeeper whose side play out from the back – and his error gifted the Saints the equaliser in the 39th minute.
Receiving the ball inside his own six-yard box, Lloris inexplicably tried a Cruyff turn with Ings closing in on him, but missed his kick and the Southampton striker's tackle saw the ball dribble over the line.
It was Lloris' ninth error leading to a goal in just over three years and surely his worst.
Given all the negativity surrounding the club this season it could have been easy for Spurs to sink, but it took them only four minutes to regain their lead.
In a move that started off with Moussa Sissoko, it took just 11 touches for the ball to end up in the back of the net as Kane flicked on a long ball, Son and Christian Eriksen exchanged passes, with the Dane then setting up the England captain to fire into the bottom corner.
Lloris was in negative equity after his first-half gaffe but went some way to getting back into credit with a couple of excellent stops after the restart.
First he tipped a curling James Ward-Prowse free-kick out with a flying save and then did even better to beat away Maya Yoshida's free header.
Southampton seemed to run out of steam and it was Spurs that found a second wind.
Kane was playing a magnificent part in a lone role and it was almost rewarded with a second goal in the final 10 minutes but he drilled an effort wide.
In the end, and perhaps surprisingly, Spurs saw it out with relative ease to produce a vital three points.