The former Birmingham man scored an incredible volley to seal a draw for Tony Pulis' side, who had to make do for much of the second half with 10 men after N'Zonzi's dismissal
Rickie Lambert's opener was cancelled out by Kenwyne Jones, but Jay Rodriguez and an Andy Wilkinson own goal gave the Saints a half-time lead.
However, Matthew Upson and Jerome's cracker snatched a point for the Potters, who also had Steven N'Zonzi sent off.
Tony Pulis was able to name nine of the XI that beat Liverpool on Boxing Day, with Upson and Ryan Shotton standing in for the suspended Ryan Shawcross and Geoff Cameron.
The Saints, meanwhile, were still without skipper Adam Lallana – who has not featured since December 8, but welcomed Rodriguez and Guly Do Prado into the starting line-up.
And it was Do Prado who made an early impact, delivering a ball into the danger area on 10 minutes, with Lambert on hand to silence the Britannia faithful and smash home his eighth of the season.
It did not take long for the Potters to hit back, however, as Jones first contrived to fire over from yards out, but quickly made amends on 16 minutes, expertly back-heeling the ball between Jos Hooiveld’s legs and past Kelvin Davis.
The visitors pressed forward, however, as Lambert whipped in a dangerous cross that forced Robert Huth into a mishit clearance. The ball rattled the crossbar, Asmir Begovic was nowhere to be seen and Rodriguez had the goal at his mercy, duly slotting home into an empty net from two yards out.
And, on 36 minutes, Stoke’s defensive nightmares deepened. A simple Jason Puncheon cross from deep entered the box and was headed down and across goal by Lambert, before Wilkinson sent the ball into his own net.
The hosts looked a shadow of the team that had been so impressive on their own patch this season, and they came out with renewed purpose in the second half, but found the Saints difficult to break down.
However, after incessant attacking, Stoke were rewarded on 65 minutes when Upson slotted home from inside the box after a corner was not cleared by the Southampton defenders.
The goal lifted the energy levels of the home players and doubled the noise levels of the home fans.
The excitement seemed too much for some, namely N’Zonzi, who lashed out with a poor challenge on Jack Cork right in front of the referee and was shown a straight red with 20 minutes remaining.
Stoke were not peturbed by the dismissal and pushed on, grabbing their reward in the 90th minute. Second-half substitute Peter Crouch knocked the ball down on the edge of the area, finding Jerome to strike a thunderous volley into the top-corner from range.