Southampton remained in the ascendancy and it was not long before the home side went in front, with Ward-Prowse matching his free kick at Manchester United last weekend with another unstoppable effort into the top corner.
Kieran Trippier is likely to miss out with a gluteal muscle strain, while Harry Winks is struggling with the groin complaint that cut short his involvement in the 1-0 midweek win at Borussia Dortmund in the second leg of the Champions League last-16 tie.
Dele Alli admits Tottenham face a "tough end to the season" after their 2-1 defeat at Southampton made it four league games without a win.
The Saints, on 27 points, are two better off than 18th-placed Cardiff in the fight against relegation.
81' - GOAL! Southampton 2-1 Tottenham: Dear me, he's done it!
And that proved costly as Southampton levelled in the 76th minute and it is not a moment Danny Rose will care to remember.
But the narrow lead came back to bite them in the second half as Southampton exerted more pressure on the Tottenham defence and two goals within a space of five minutes won the three points for the home side.
James Ward-Prowse free-kick caps Saints comeback against Tottenham
And ultimately they were successful as Yan Valery equalised and James Ward-Prowse struck the victor with a curling free-kick nine minutes from full time.
But someone was - Valery, who struck from close range to secure his second goal in two games following his stunning strike against Manchester United last week.
It may be a cliche but sometimes football really is a game of two halves.
Mauricio Pochettino, who was condemned to a seat in the stands following his touchline ban, will be furious with what he had to watch in the second half, but he could not have imagined it panning out that way.
The visitors had held the lead at half-time through Harry Kane's opener and fully deserved their advantage following dominant first 45 minutes.
Spurs' bid for the 2016 title had also been undermined by inexperience when they dropped points in a defining fixture against rivals Chelsea, and the Argentinian said: "That is experience, through learning through history; competing in that level is not the same".
Cardiff, though, gave themselves hope as early goals in each half from Junior Hoilett and Victor Camarasa gave the Welsh side a precious three points over a hugely disappointing West Ham.
However, Knockaert sparked wild celebrations from the Brighton fans when he curled into the top corner the victor 16 minutes from time.
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