Salisu scored a comedy own goal in the second half as Spurs ran out 4-1 winners at the Tottenham Hotspur Stadium.
Southampton took the lead early on through James Ward-Prowse but were quickly pegged back, Ryan Sessegnon equalising for the home side less than 10 minutes later.
Antonio Conte's side then took the lead before half-time, Eric Dier heading in Son Heung-min's cross to put the hosts ahead.
On the hour mark, Tottenham took a two-goal lead through some calamitous defending from Salisu.
After Emerson Royal had played a hopeful pass across the face of goal, Salisu made a mess of his clearance and somehow managed to turn the ball into his own net despite being under no pressure from an opposition player.
Tottenham would score again just three minutes later through Dejan Kulusevski as Conte's side ran out comfortable winners.
And it was Salisu's horrific mistake that had fans talking after the match.
"How is this Salisu a pro?? He makes this kind of mistake every 3 games," wrote one angry supporter on Twitter.
It might only be the first weekend, but that Mohammed Salisu finish could easily be the worst own goal we see all season— FootballJOE (@FootballJOE) August 6, 2022
SALISU WHAT A FINISH— 🇸🇪 (@axelthfc) August 6, 2022
That’s one of the funniest own goals I’ve seen from Salisu, absolutely shocking defending 😭😭😭— ®️Ⓜ️🐝 (@rianmbfc) August 6, 2022
Another added: "That's a shocker from Salisu, the ball was going out ffs."
A third wrote: "That’s one of the funniest own goals I’ve seen from Salisu, absolutely shocking defending."
Salisu and Southampton will hope to bounce back quickly from the defeat when they face Leeds United next Saturday.
Meanwhile, Tottenham - the Premier League's early leaders - take on London rivals Chelsea next Sunday.
Featured Image Credit: Premier League