It looked like Frederic Veseli's 89th-minute half-volley had consigned Martin Hunter's men to a heartbreaking defeat at Altrincham's Moss Lane ground.
But Calum Chambers came to Saints' rescue with a low drive that squirmed past United goalkeeper Pierluigi Gollini deep into injury time.
The visitors had trailed at the break to Jesse Lingard's third-minute opener, but responded well and seized the lead through two headers in the space of five second-half minutes from Jake Sinclair.
It looked like the game was set for a two-all draw until late intervention from Veseli, but Chambers' goal ensured Saints took the point their performance warranted back to the south coast.
U21 Coach Hunter selected overage players Artur Boruc, Dan Seaborne and Steve De Ridder in his starting line-up, while Chambers and Jack Stephens also started following international duty with England's Under-19s.
It was a nightmare start for Saints, though, as United frontman Joshua King twisted and turned before teeing up Lingard to dispatch a heavily deflected shot past Boruc after just three minutes.
The visitors began to find their feet without quite troubling the United defence, while the hosts had a half-chance on the quarter-hour when Bebe lashed a shot wide of the goal.
The Angolan had an even better opportunity with 20 minutes gone at the end of a rapid United break, but Boruc came to Saints' rescue by saving excellently with his legs.
That counter-attack stemmed from an unsuccessful Southampton corner, which was awarded after Ben Reeves' free-kick had deflected narrowly over.
Hunter's team continued to build, though, with De Ridder seeing a shot held by goalkeeper Gollini before Reeves fizzed a drive just over the Italian's crossbar.
Lingard went close to adding his second five minutes before the break with a fierce left-footer, but Boruc was alert to tip his shot over the bar for a corner which Saints scrambled clear.
The visitors could well have levelled a few minutes before the break as they broke down the left through De Ridder, but the Belgian's drive ended up the wrong side of the crossbar.
There was time for another chance on the stroke of half-time, too, as Reeves saw a fierce shot gathered by Gollini.
HALF TIME: MAN UTD U21 1-0 SAINTS U21
The visitors continued to pressurise after the break, though they had Boruc to thank again five minutes into the second period when he held Tom Thorpe's back-post volley from a corner.
Lingard then curled a nice shot over Boruc's bar, prompting Hunter to bring on Corby Moore in place of Joe Curtis just before the hour mark.
But Saints did finally find their leveller on 62 minutes when Reeves' cross from the left found the head of SINCLAIR, who rose majestically to head inside the far post to make it one-all.
And winger SINCLAIR – who was perhaps the shortest man on the pitch – added a second just four minutes later in a nigh-on identical situation as he headed home inside the six-yard box.
But the lead was short-lived as United got themselves back on level terms on 70 minutes as Cole interchanged passes on the right of the area before firing across goal and inside the far post.
After three goals in just eight minutes, both sides began to settle back down as the game entered its final stages.
Saints brought on Alberto Seidi – called into the Portugal Under-21 squad last week – in place of double goalscorer Sinclair nine minutes from time as they went in search of a dramatic winner.
But it was United who looked to have snatched all three points as King got free down the left before centring low across the face of goal for Veseli to smash in with just a minute left on the clock.
However, Saints had the last say as the ball broke for CHAMBERS on the edge of the box in the last of the four added minutes, and his shot squirmed past Gollini to make it 3-3 with the final kick of the game.
The result sees the Under-21s drop to third place in National Group 2 of the Barclays Under-21 League after Newcastle jumped into second having beaten Aston Villa 2-1. However, there are just three points between group leaders and Saints ahead of the next round of fixtures.
FULL TIME: MAN UTD U21 3-3 SAINTS U21
Man Utd U21: Gollini, Wootton, Blackett (McGinty 67), Thorpe (c), M. Keane, Fornasier, Bebe (Veseli 78), Cole, King (James 90+3), Tunnicliffe, Lingard. Substitutes: Pereira (GK), Hendrie.
Goals: Lingard (3), Cole (70), Veseli (89)
Saints U21: Boruc, Young, Stephens, Seaborne, Shaw, Curtis (Moore 59), Chambers, Reeves (c), Sinclair (Seidi 81), Hoskins, De Ridder. Substitutes: Britt (GK), Turnbull, Isgrove.
Goals: Sinclair (62 & 66), Chambers (90+4)
Referee: Steven Copeland
Assistant Referees: Mike Jones & Thomas Kirk
Fourth Official: Michael Johnson