The Blues took an early lead via a Taylor Harwood-Bellis own goal but Jay Robinson levelled for Southampton to leave the scoreline 1-1 at half-time at Portman Road.
Town made one change from the team which opened the season at Birmingham nine days ago with Jaden Philogene making his first appearance of the season following the ankle injury he suffered at Auxerre in the final friendly.
The former Hull City and Aston Villa man came into the team for Chieo Ogbene, who dropped to the bench, starting on the left with Jack Clarke switching to the right. Sammie Szmodics was the number 10 and George Hirst the out-and-out striker.
Azor Matusiwa made his home debut in the centre of midfield alongside Jack Taylor, while Ben Johnson, skipper Dara O’Shea, Jacob Greaves and Leif Davis were again the back four behind keeper Alex Palmer.
Jens Cajuste was on the bench for the first time since returning to the club, but there was no place for Chuba Akpom, who felt some muscle tightness in training in the week.
Ali Al-Hamadi dropped out of the 20-man squad with youngster Leon Ayinde on the bench for a league game for the first time.
Southampton made two changes from the team which beat Wrexham 2-1 on the opening day with England defender Harwood-Bellis, who returned from injury in the 1-0 Carabao Cup victory over Northampton in the week, and the West Ham-linked Mateus Fernandes coming in for Ronnie Edwards and Yuki Sugawara, who were among the subs.
Also on the bench was highly rated youngster Tyler Dibling, who had looked set to join Everton, while Damion Downs and Ross Stewart were absent due to illness.
Former Blues midfielder Flynn Downes started alongside ex-loanee Ryan Fraser with one-time Town loan keeper Alex McCarthy on the bench.
With the home crowd having given them a big welcome as they made their way onto the pitch, Town started brightly with Davis and Clarke sending crosses in from either flank in the third minute with the Saints defence looking at sixes and sevens.
And the fourth minute, the Blues went in front. Szmodics forced an error on the Town right with tight pressing, Welington played a pass back to Joshua Quarshie, who let it run behind him on the edge of his own area, allowing Hirst to nip in ahead of him and gain possession.
The Scotland international was at too tight an angle to shoot but was able to cut back to Clarke, whose mis-hit effort was going a long way wide until Harwood-Bellis diverted it into his own net with his arm.
After defending a couple of corners at the other end, the Blues, with the home fans continuing to make a noise, went close to a second from a flag-kick of their own on the left at the other, Hirst rising highest but flicking his header beyond the far post.
There was a scare for the Blues in the 18th minute when Adam Armstrong moved the ball across the area to Welington in space on the left but Robinson got in his teammate’s way and the ball ended up bobbling well wide.
Southampton were starting to get more into it after a shaky start, however, and on 20 Greaves made a not overly comfortable clearance from a ball into the area and a minute later O’Shea turned a cross from the left behind.
On 23, Shea Charles was very fortunate to avoid a yellow card after clattering into the back of Matusiwa’s ankles just inside the Town half, the Dutchman’s cry of anguish having been audible from the stands.
From the free-kick, Taylor played a ball over the Saints’ defence to Szmodics on the left of the area, the forward failing to get a clean contact and the ball bouncing wide. The former Blackburn man landed awkwardly on his left knee and needed treatment as a result but was OK to continue, much to the relief of the home support.
In the 29th minute, Greaves brought the ball out from the back before losing possession midway inside the Saints’ half. And from the subsequent break the visitors equalised.
Davis was unable to get on a ball out to Fraser on the right and the ex-Blues loanee had a free run down the flank. His first low cross was blocked by Taylor but it was played back to him by Fernandes and the Scot crossed to the edge of the six-yard area and Robinson headed down and past Palmer.
It was a poor goal from a Town perspective with Greaves stepping out having left them short as Southampton counter-attacked.
On 34, Downes fouled Davis on the Blues’ left, the full-back sending over a deep free-kick which O’Shea nodded back across goal, keeper Gavin Bazunu needing to backpedal to claim on his line. The linesman raised his flag, although with video footage showed that the Irishman was well onside.
Five minutes later, Philogene won the ball on halfway, sending Hirst away. The striker took it on past two defenders before hitting a low shot which Bazunu blocked when Clarke to his right was a better option.
Southampton quickly turned defence into attack, forcing Palmer out of his goal to midway inside Town’s half where he momentarily looked to be in trouble under pressure but O’Shea cleared.
Saints right wing-back Welington was shown the game’s first yellow card in the 41st minute for the latest in a succession of fouls on Clarke after the ball had gone, Charles having taken a similar approach on Matusiwa without referee Bobby Madley taking similar action.
Taylor joined the Brazilian international in the book soon afterwards having skipped past a number of defenders before Harwood-Bellis blocked the former Posh midfielder. The Irish international managed to stay on the ball but was penalised for man-handling the defender by referee Madley, then was cautioned for his frustrated reaction, much to the anger of the Portman Road support.
Matusiwa joined his fellow midfielder in Madley’s book for a foul on Charles as the half moved into injury time, the ex-Reims man clearly feeling he’d been hard done by given some of Charles’s early challenges on him.
That was the last action of a half which had started very positively for the Blues, grabbing an important early goal having got on top in the early stages.
However, Southampton had come into the game more as the half wore on and deserved their equaliser.
Clear-cut chances continued to be rare at both ends but with the Saints more in control in the latter stages.
Town: Palmer, Johnson, O’Shea (c), Greaves, Davis, Matusiwa, Taylor, Clarke, Szmodics, Philogene, Hirst. Subs: Walton, Kipre, Woolfenden, Chaplin, Cajuste, Young, Ogbene, Humphreys, Ayinde.
Southampton: Bazunu, Fraser, Harwood-Bellis, Stephens (c), Quarshie, Welington, Downes, Charles, Fernandes, Robinson, Armstrong. Subs: McCarthy, Manning, Edwards, Wood, Sugawara, Archer, Brereton-Diaz, Matsuki, Dibling. Referee: Bobby Madley (West Yorkshire).