Spurs went ahead through Harry Kane's 200th career goal for club and country.
But quick-fire goals from Saints pair Yan Valery and Ward-Prowse in the final 15 minutes dented Spurs' top-four ambitions, while keeping the struggling hosts out of the drop zone.
Ward-Prowse said, “It's a big win. I don't think anyone expected us to get anything today but with the belief that we showed and the character in the second-half, that epitomises everything the manager has brought into the team and the club. That's the Southampton we know.
“Spurs are without doubt a quality team and we knew they were going to have a lot of possession but I think we were a bit passive and brought them on to us and we were lucky to go in to the break just the one goal down.
“We saw that as an opportunity and you could feel the game coming back into our hands in the second-half. I think we were very clinical and I think the lads who came on made a big difference as well, so all in all a really good performance."