Jake Sinclair and Lloyd Isgrove each scored their third goals of the season to put their team well in control at Molineux before Liam McAlinden halved the deficit with 58 minutes gone.
Having dominated the first hour, Saints had to work hard to protect their lead until the hosts were reduced to ten men in the closing stages after Michael Ihiekwe was booked twice in the space of ten minutes.
But, deep into injury time, referee Michael D'Aguilar harshly penalised Calum Chambers for handball in the area and Matt Doherty duly dispatched his 95th-minute spot kick to make it two-all.
The game was in some doubt earlier in the day due to overnight snowfall in the Black Country but it went ahead after the venue was switched from Telford United's New Bucks Head ground.
Martin Hunter made two changes to the team that lost 3-1 to Manchester United nine days ago, giving goalkeeper Paulo Gazzaniga his first U21 involvement in place of Cody Cropper while James Ward-Prowse came in for Corby Moore.
Gazzaniga lined up behind a defence consisting of Chambers, Aaron Martin, Jordan Turnbull and Matt Targett, while Ward-Prowse was joined in midfield by Joe Curtis and captain Jack Stephens.
Saints' pace-filled frontline was made up of Sinclair down the middle with Omar Rowe on the left flank and Isgrove on the right.
After a quiet opening, the game's first flashpoint came after ten minutes when Curtis went to ground in the Wolves box as he looked to round goalkeeper, Jonathan Flatt but referee D'Aguilar was unconvinced by his appeals for a spot kick.
But Saints did take a 16th-minute lead when, after Rowe's shot had been blocked by Wolves defender Jamie Tank, the ball eventually made its way to SINCLAIR to audaciously back-heel past Flatt and inside the far post.
Hunter's men could have added a second barely a minute later when a low delivery from the right flashed across the face of goal, but no-one was on hand to force the ball home.
The hosts looked to respond but found Martin and Turnbull in good form at the heart of the Southampton defence, meaning Gazzaniga was a virtual bystander for much of the first period.
Meanwhile, at the other end, the pace of Sinclair and Rowe looked a constant threat but concrete chances remained at a premium as the game approached its half-time interval.
Saints could well have added a second ten minutes before the break after Rowe dispossessed opposing centre-half Tank, but the wide-man was denied by Flatt's excellent double-save.
HALF TIME: WOLVES U21S 0-1 SAINTS U21S
Their second goal would duly arrive three minutes into the second period when ISGROVE picked the ball up on the right and drove at the Wolves defence before squeezing his shot underneath the opposition goalkeeper from a few yards out.
With Saints well in control, the hosts were allowed a lifeline just before the hour when McAlinden stooped to head Jack Price's right-sided cross past Gazzaniga to make it 2-1.
Wolves had an opportunity to equalise on 65 minutes when a corner from the right was met by the head of defender Michael Ihiekwe, but his effort dropped wide of the Saints goal.
Sinclair could well have restored his side's two goal cushion four minutes later but, after picking up Chambers' cut back and turning onto his left foot, his shot was superbly parried away by Flatt.
Soon afterwards, the impressive Rowe went close after twisting and turning in the Wolves box only to last his shot wide of the post from a good position.
Isgrove then looked to have got in on goal after smartly knocking the ball past Jamie Reckord only to be floored by Ihiekwe just outside the box, with Ward-Prowse's subsequent free-kick easily saved by Flatt.
Wolves had to play the final eight minutes of normal time with ten men after Ihiekwe was shown an 82nd-minute red card for bringing down Isgrove again to end a Saints counter-attack.
Another rapid break offered the visitors a chance to add a third when Isgrove got free down the left, but he was again denied by goalkeeper Flatt.
Wolves had an opportunity to equalise deep into injury time when the ball fell to Anthony Forde, but his shot was superbly charged down by left-back Targett.
But there was still time for one cruel twist in the game as McAlinden's cross bounced off Chambers just inside the Saints box, leading D'Aguilar to penalise the full-back for an apparent handball.
The decision was met with general incredulity and bemusement but, nevertheless, Doherty stepped up to send Gazzaniga the wrong way and level with practically the final kick of the game.
FULL TIME: WOLVES U21S 2-2 SAINTS U21S
Wolves U21s: Flatt, Doherty, Tank, Ihiekwe (c), Reckord, Ismail (Parry 59), Evans, Price, Forde, Cassidy, McAlinden. Subs (not used): McCarey (GK), Jakobsson, Cranston, Whittall.
Goals: McAlinden (58)
Bookings: Price (22)
Sent off: Ihiekwe (82)
Saints U21s: Gazzaniga, Chambers, Martin, Turnbull, Targett, Stephens (c), Ward-Prowse, Curtis, Isgrove, Sinclair, Rowe. Subs (not used): Cropper (GK), Gape, Young, Ariyibi, Moore.
Goals: Sinclair (16), Isgrove (48)
Bookings: Ward-Prowse (76), Gazzaniga (84), Martin (90+4)
Referee: Michael D'Aguilar