Cameron Jerome's stunning late equaliser denied Southampton and preserved 10-man Stoke's unbeaten record.
Substitute Jerome lashed into the top corner from 30 yards to rescue City after a poor first-half display saw them slip 3-1 behind.
Three times Saints took advantage of confusion in a City defence that was without suspended pair Ryan Shawcross and Geoff Cameron.
Rickie Lambert opened the scoring at the far post and, after Kenwyne Jones' backheeled equaliser, Jay Rodriguez profited from a mix-up, with Andy Wilkinson turning into his own net for the third.
The visitors should have made the game safe early in the second half, only for Guly do Prado to miss from the edge of the 18-yard box with the Stoke goal unguarded.
"This was one of the most entertaining matches of the season. Stoke showed they never know when they are beaten, and that last-gasp draw makes it 17 games undefeated at home in the league. For Southampton, who led for so long, what will those two dropped points mean at the end of the season?"
It was to prove a crucial moment as, soon after, Matthew Upson scrambled home from a corner.
With Stoke down to 10 following Steven Nzonzi's red card for a studs-up challenge on Jack Cork, Jerome produced his moment of brilliance to extend their unbeaten run to 10 games.
It was perhaps cruel on Saints, who fully deserved their half-time lead, but Stoke can justifiably claim they deserved a point for the way they battled in a second half. They had two penalty appeals turned down when Jose Fonte and Maya Yoshida appeared to have handled.
The Potters may be concerned, though, at the way the tightest defence in the Premier League was so easily breached without the presence of Cameron and, more importantly, Shawcross.
Nigel Adkins opted to partner Lambert with Rodriguez up front and, with Do Prado and Jason Puncheon impressing on the flanks, the Southampton manager's positive approach was vindicated.
Saints deservedly took the lead as Do Prado turned Ryan Shotton - in for Cameron at right-back - and crossed for Lambert to get ahead of Wilkinson and slot home.
Stoke hit back almost immediately, with Shotton making amends to jink past Luke Shaw and square for Jones, whose cool backheel crept inside Kelvin Davis's far post.
But, from there, Stoke fell apart. First Lambert had time to collect a long ball, turn and float a cross into the box. Goalkeeper Asmir Begovic looked to have it covered, only for Robert Huth to deflect the ball onto his own bar, with Rodriguez able to tap into the empty net.
It got worse for the Potters when Puncheon collected the ball from a corner and delivered a cross that was turned past Begovic by Wilkinson after Lambert's knock-down.
Stoke improved after the break, but they should have been put out of the game, only for Do Prado to miss with the goal at his mercy. It was to be Saints' last real chance.
Upson pulled one back as the ball bounced around the Saints box, with Stoke then aggrieved as Mark Clattenburg waved away appeals for a penalty when Fonte looked to have handled as Jones jumped for a header.
The hosts' sense of injustice deepened when Nzonzi saw red, but Cork was arguably lucky to escape injury from the Frenchman's lunge.
Even though they were a man down, City continued to press, with boss Tony Pulis deciding that four of his 10 men should be strikers.
Jerome and Peter Crouch joined the action and after more scrambling in the Saints' box and the appeal against Yoshida, Stoke were finally rewarded for their spirit and persistence.
Jerome pounced on Crouch's knock-down to fire high past Davis to complete a breathless afternoon at the Britannia.
Stoke manager Tony Pulis: "I thought we were awful in the first half. That's as bad as we've been. We were poor defensively and gave poor goals away, and we looked off the pace. We were slapping ourselves on the back after the Liverpool game.
"But we ended up playing with a lot of commitment and desire and we think, even with 10 men, we should have won the match. It was a fantastic game for the supporters, but not for the manager."
Southampton boss Nigel Adkins: "Stoke have only conceded four at home all season, so for us to have scored three is outstanding for us. We weathered a storm and it took a wonder-strike for Stoke to get a point. We are always positive and we can always score goals.
"We have matured all season and it's excellent to win a point at Stoke. We have a team that are showing a great character and a great desire to do well in this division."
Live Text Commentary
Full Time The referee signals the end of the game.90:00 +5:37
Jack Cork challenges Dean Whitehead unfairly and gives away a free kick. Glenn Whelan delivers the ball, Peter Crouch takes a shot. Save made by Kelvin Davis.89:35
The assist for the goal came from Peter Crouch.89:35 Goal scored
Goal! - Cameron Jerome - Stoke 3 - 3 Southamp'n Cameron Jerome fires in a goal from a long way out to the top right corner of the goal. Stoke 3-3 Southampton.87:05
The referee blows for offside. Kelvin Davis takes the indirect free kick.85:28
Corner taken by Glenn Whelan.85:13 Booking
Booking Caution for Cameron Jerome.84:15 Substitution
Substitution Frazer Richardson replaces Jason Puncheon.81:21 Substitution
Substitution Daniel Fox joins the action as a substitute, replacing Luke Shaw.78:33
Corner taken by Glenn Whelan played to the near post.77:23
Asmir Begovic restarts play with the free kick.77:23 Booking
Booking The referee cautions Jay Rodriguez for unsporting behaviour.77:18
Robert Huth fouled by Rickie Lambert, the ref awards a free kick.76:56
Kenwyne Jones takes a shot. Save by Kelvin Davis.74:30 Substitution
Substitution Peter Crouch replaces Michael Kightly.73:41
Shot on goal by Kenwyne Jones from just inside the area goes over the target.72:16
The referee blows for offside. Free kick taken by Asmir Begovic.70:33
Jos Hooiveld takes the free kick.70:33 Dismissal
Dismissal Steven Nzonzi sent from the field by the ref for serious foul play.70:27
Free kick awarded for an unfair challenge on Jack Cork by Steven Nzonzi.
Substitution Dean Whitehead on for Andy Wilkinson.66:26
Assist on the goal came from Kenwyne Jones.66:26 Goal scored
Goal! - Matthew Upson - Stoke 2 - 3 Southamp'n Matthew Upson grabs a goal from inside the penalty area low into the middle of the goal. Stoke 2-3 Southampton.66:13
Outswinging corner taken from the right by-line by Glenn Whelan. Kenwyne Jones takes a shot. Jose Fonte gets a block in.65:35
Effort from inside the area by Guly Do Prado misses to the left of the goal.65:18
Jay Rodriguez takes a shot. Save made by Asmir Begovic.62:52
Jay Rodriguez takes a shot. Robert Huth gets a block in.61:12
Jos Hooiveld fouled by Kenwyne Jones, the ref awards a free kick. Kelvin Davis restarts play with the free kick.60:43
Outswinging corner taken by Glenn Whelan from the right by-line played to the near post.60:18
Outswinging corner taken by Glenn Whelan from the right by-line, clearance made by Jos Hooiveld.58:01
Outswinging corner taken from the right by-line by Glenn Whelan.56:38
Foul by Jonathan Walters on Luke Shaw, free kick awarded. Kelvin Davis restarts play with the free kick.56:13 Substitution
Substitution Cameron Jerome comes on in place of Matthew Etherington.51:59
Michael Kightly takes a shot. Save by Kelvin Davis.49:55
Jonathan Walters takes a shot. Blocked by Jos Hooiveld.48:45
Unfair challenge on Robert Huth by Rickie Lambert results in a free kick. Direct free kick taken by Asmir Begovic.48:01
Short corner taken by Jason Puncheon from the right by-line.46:46
Free kick crossed by Jonathan Walters.46:46 Booking
Booking Booking for Jose Fonte for unsporting behaviour.46:45
Unfair challenge on Jonathan Walters by Jose Fonte results in a free kick.45:01
The referee gets the second half underway.45:00 +2:16 Half time
Half Time The referee blows for half time.45:00 +1:47
Matthew Etherington challenges Maya Yoshida unfairly and gives away a free kick.45:00 +0:42
The assistant referee signals for offside against Jay Rodriguez. Matthew Upson restarts play with the free kick.44:00
A cross is delivered by Ryan Shotton, Jos Hooiveld makes a clearance.43:11
Free kick awarded for a foul by Luke Shaw on Michael Kightly. Robert Huth takes the free kick.38:33
Jack Cork takes a shot. Save by Asmir Begovic.35:41
Assist by Rickie Lambert.35:41 Goal scored
Goal! - Andy Wilkinson - Stoke 1 - 3 Southamp'n An own goal is conceded by Andy Wilkinson. Stoke 1-3 Southampton.35:01
Corner taken right-footed by Guly Do Prado from the left by-line, clearance by Steven Nzonzi.34:31
Kenwyne Jones challenges Maya Yoshida unfairly and gives away a free kick. Jason Puncheon takes the direct free kick.28:58
Maya Yoshida concedes a free kick for a foul on Matthew Etherington. Glenn Whelan takes the free kick.28:37
Jos Hooiveld gives away a free kick for an unfair challenge on Kenwyne Jones. Asmir Begovic takes the free kick.27:51
Corner taken left-footed by Jason Puncheon, Kenwyne Jones manages to make a clearance.27:34
Jason Puncheon takes a shot. Save by Asmir Begovic.26:02
Corner taken by Jason Puncheon from the right by-line to the near post, Matthew Upson manages to make a clearance.25:17
Jason Puncheon takes a shot. Blocked by Matthew Upson.24:42
Foul by Guly Do Prado on Kenwyne Jones, free kick awarded. Ryan Shotton takes the free kick.23:36
Rickie Lambert provided the assist for the goal.23:36 Goal scored
Goal! - Jay Rodriguez - Stoke 1 - 2 Southamp'n Jay Rodriguez finds the back of the net with a goal from close in high into the middle of the goal. Stoke 1-2 Southampton.21:34
Corner from the right by-line taken by Matthew Etherington, Guly Do Prado makes a clearance.19:58
Foul by Robert Huth on Jay Rodriguez, free kick awarded. Free kick crossed right-footed by Guly Do Prado, Asmir Begovic makes a save.15:05
Ryan Shotton provided the assist for the goal.15:05 Goal scored
Goal! - Kenwyne Jones - Stoke 1 - 1 Southamp'n Kenwyne Jones fires in a goal from close in to the bottom left corner of the goal. Stoke 1-1 Southampton.15:04
A cross is delivered by Ryan Shotton,13:54
Free kick awarded for an unfair challenge on Jonathan Walters by Morgan Schneiderlin. Direct free kick taken by Asmir Begovic.12:18
The referee blows for offside against Jay Rodriguez. Indirect free kick taken by Asmir Begovic.11:03
Shot on goal by Kenwyne Jones from inside the box goes harmlessly over the target.9:17
Guly Do Prado provided the assist for the goal.9:17 Goal scored
Goal! - Rickie Lambert - Stoke 0 - 1 Southamp'n Rickie Lambert fires in a goal from close range low into the middle of the goal. Stoke 0-1 Southampton.9:16
Centre by Guly Do Prado,6:04
The assistant referee signals for offside against Rickie Lambert. Robert Huth restarts play with the free kick.0:00
The referee gets the game underway.
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