The Gunners, who lost their premier league title two weeks ago and whose Champions League dreams faded in March, rescued their season from anti-climax with their ninth FA Cup win in a record 16th final appearance.
It needed a goal-line clearance from a James Beattie header deep in stoppage time to ensure Arsenal retained the trophy they won 12 months ago against Chelsea.
Pires scored with a shot on the turn after 38 minutes and although the Saints battled feverishly throughout, Arsenal were always just a little too classy.
Manager Arsene Wenger spoke of his relief at ending the season with some silverware.
"The team was under immense pressure because they risked finishing without a trophy," he said. "The group got a big blow when we lost the championship.
"Not only are they great players but they have great spirit. I felt we got a very important victory."
Southampton manager Gordon Strachan could not fault his side's effort.
"We had chances and couldn't take them but we did very well. I am very proud of the way they competed," he said. "We had huge hearts and battled for every ball. There are no regrets."
The Cup triumph was Arsenal's third under Wenger in six seasons and they moved to within one win of Manchester United's all-time record of 10.
They also emulated the achievements of their old rivals Tottenham Hotspur, the last club to retain the FA Cup in both 1962 and 1982.
TOUGH CAUSE
The Saints' already tough cause was not helped when their giant Finnish goalkeeper Antti Niemi pulled a muscle taking a goal-kick and was taken off on a stretcher after 66 minutes to be replaced by Paul Jones. It was the first goalkeeping substitution in FA Cup final history.
At the other end, David Seaman, at 39 the oldest goalkeeper to play in the Cup Final and the third oldest player ever, had a safe match, collecting his fourth FA Cup winners' medal in what could be his last game for the club.
Captaining his side to victory -- only the second goalkeeper in FA Cup history to do so -- he made one outstanding save from Brett Ormerod after 84 minutes but did not have much else to do. He had Ashley Cole to thank for keeping out Beattie's goalbound header after 94 minutes when the England defender cleared the ball off the line.
Arsenal, without injured skipper Patrick Vieira and suspended defender Sol Campbell, could have gone ahead as early as the 23rd second. Henry had a chance to score the fastest goal in cup final history when he broke clear, only for Niemi to save with his legs.
Arsenal gradually took control for long periods of the half, but Southampton, with Wayne Bridge overlapping well and their skipper Chris Marsden looking to get forward at every opportunity, had more than matched them when the Gunners scored following their best move of the half.
PERFECTLY WEIGHTED
Ray Parlour started it with a pass to Henry on the right and the footballer of the tear played a perfectly weighted pass to the overlapping Dennis Bergkamp who slipped another good ball inside to Freddie Ljungberg.
The Swede's attempt was blocked but the ball ran loose to Pires who made the most of his break. The French midfielder controlled instantly and shot low on the turn, the ball brushing Niemi's outstretched hand on its way into the net.
Southampton's Chris Baird, a surprise selection at right back in place of Fabrice Fernandes, then cleared a Bergkamp effort away from the line.
The Saints, looking to win the FA Cup for the first time since 1976, were causing problems of their own and Beattie was only marginally offside before putting the ball in the net after 21 minutes.
That was the closest they came to a goal all afternoon, but at least they were left with the huge consolation prize of a UEFA Cup place.
Arsenal will have another crack at the Champions League and begin next season looking to become the first club to win the FA Cup three years in succession since Blackburn Rovers in 1884, 1885 and 1886.
