Home-grown Andrew Surman was Southampton's hero, scoring once and making two others after Stoke had gone ahead.
It was typical of Southampton's recent misfortunes that the man who put Stoke ahead in the tenth minute was Jamaican international Ricardo Fuller, who held off Darren Powell before scoring with a right-foot shot.
Saints manager George Burley left out transfer-seeking Kenwyne Jones, who is on the brink of a move to either Sunderland or Derby County next week.
But they made light of his absence by equalising in the 36th minute. Youssef Safri set it up and Surman scored with a low left-foot shot from the edge of the area.
Both sides had the chance to be ahead by half-time and a header from Ryan Shawcross seemed to have crossed the line when Rudi Skacel headed clear from under the bar.
But it was Southampton that went ahead in the 71st minute and again Surman was involved, jinking past two tackles on the left of the area before floating a perfect centre for Poland international striker Grzegorz Rasiak to head home from 12 yards for his second of the season.
Southampton looked to have sealed an impressive win in the 75th minute when Shawcross could only head another dangerous centre from Surman into the path of Jhon Viafara, who miscontrolled before beating Steve Simonsen with a low right-foot shot.
Stoke manager Tony Pulis sent on three substitutes, including his 20-year-old son Anthony Pulis, but it was another of his replacements Jon Parkin who set up an exciting finish by heading home an 82nd minute corner.