Saints – playing their second Barclays U21 Premier League Elite Group game – travelled to the Hotspur Way Training Centre having seen last week's home match against Arsenal postponed.
But things did not get off to an ideal start as Shaq Coulthirst gave the home side an 11th-minute lead with a close-range header.
Spurs – who beat Saints 4-2 and 4-0 in the first half of the season – doubled their advantage three minutes later when Alex Pritchard drove in from a narrow angle.
But Martin Hunter's men responded well, forcing a number of corner kicks as they set about clawing Tottenham back.
Their breakthrough arrived with 41 minutes on the clock as Jake Sinclair's corner was only partially cleared, allowing captain BEN REEVES to power home for 2-1.
Southampton continued to battle towards a leveller after the interval and got their rewards just after the hour when the impressive Matt Targett threaded REEVES through to finish confidently past Jonathan Miles.
Both sides went in search of a winning goal during the last half-hour, but the game finished with the scoreline tied at 2-2.
"On the whole, I'm very pleased," U21 Coach Hunter told saintsfc.co.uk
after the match.
"We started the game very brightly but conceded two poor goals from not defending crosses properly with them coming down our right side.
"After that, we've dominated the game. We had at eight-to-ten corners in the first half, which shows how well we did.
"We talked about a couple of things in the half-time break in terms of our defending and, as the second half went on, we played better and better.
"The most pleasing thing was how we pressed Spurs' team and really knocked them out of their rhythm. In terms of our passing and movement, we could well have won it."
Hunter made a number of changes from his team's last game, a 1-0 loss at Liverpool 12 days ago.
Jack Stephens was given a run-out in midfield with Calum Chambers moving to right-back, allowing Aaron Martin to appear as an overaged player following the end of his loan spell at Crystal Palace.
Jonathan Forte was also added to the starting team in place of Lloyd Isgrove, and the coach was particularly pleased with how his overaged players fared.
Hunter said: "Again, the senior players in the team were excellent in terms of their work-rate and the way they conducted themselves with the younger players.
"This under-21 league is now a test, and it means the senior players in it get a real good work-out. That's a massive value for the club.
"Aaron Martin played well and helped the young players in the back-line, and Jordan Turnbull had his best defensive game.
"We tried one-or-two things that were positive. We've played Jack Stephens in midfield because we're looking at positions that he may be able to play.
"We're now going to prepare for Manchester United next Saturday, which will be a good game."
Spurs U21s: Miles, Fredericks (Stewart 87), Gallifuoco, Veljkovic, Barthram (Byrne 63), Luongo, Mason (Bostock 63), Ceballos, Coulthirst, Pritchard. Sub (not used): McGee (GK).
Southampton U21s: Cropper, Chambers, Martin, Turnbull, Targett, Stephens, Moore, Reeves, Sinclair (Isgrove 73), Barnard, Forte. Subs (not used): Johns (GK), Seidi, Young, Curtis.