With rivals Spurs losing at home to Brighton earlier in the day, Arsenal had the opportunity to reach 57 points and boast a game in hand over their neighbours. However, despite a promising start to the game and a strong finish, there was a lack of urgency about Mikel Arteta's men given the challenge at hand. Jan Bednarek scored the decisive goal against the run of play and moments before half-time when he lashed home from close range following clever work from Mohamed Elyounoussi.
Arsenal had earlier wasted two good chances to break the deadlock before then, with Saints keeper Fraser Forster making two excellent saves to deny the visitors. Forster first dived low to his right to deny Gabriel Martinelli and then high to his right to thwart Bukayo Saka -- who really should have done better -- from close range.
Forster then proved just as difficult to beat in the second half, with Eddie Nketiah, Saka and Granit Xhaka all coming close.
It's now three defeats in a row for Arteta's men, and advantage Manchester United in the race for the elusive Champions League spot.
Arsenal started brightly and dominated possession, carving out two goal-scoring chances early. The Gunners then enjoyed 80% possession at the start of the second half, 76% overall.
Arsenal will be kicking themselves for failing to build on a bright start. They were guilty of wasting good chances before seemingly running out of steam. They threatened late, but it was too little too late.
Manager rating out of 10
5 -- Mikel Arteta started with Saka on the left and Martinelli on the right, which didn't seem to get the best out of either player. Moreover, he persisted with Cedric on set pieces, which seemed odd given the outcome every time he took one. Arteta then switched to a back three as he chased the game and while Arsenal ramped up the pressure on the home side, they couldn't regain parity.
Player ratings (1-10; 10 = best, players introduced after 70 minutes get no rating)
GK Aaron Ramsdale, 5 -- The goalkeeper had very little to do as Arsenal dominated possession in front of him for the first half-hour. His first major contribution was to pick the ball out of his net; the England international got a hand to Bednarek's effort, but couldn't keep it out.
DF Ben White, 5 -- Struggled to keep pace with Armando Broja in the opening exchanges. He was also guilty of slowing the play down at times when he brought the ball out of defence, and that didn't change when he moved forward in Arteta's second-half reshuffle.
DF Gabriel Magalhaes, 6 -- The defender was guilty of playing the Saints forwards online moments before they scored. However, he was one of the few Arsenal players to try to break the lines with his distribution.
DF Cedric Soares, 4 -- Returned to St Mary's but only to ironic jeers. His first free-kick went straight into the side netting from a promising position, his second went over the bar. A poor performance.
MF Martin Odegaard, 5 -- A disappointing afternoon from the skipper, who failed to create much of note in the final third until a scuffed shot late in the game from the edge of the area.
MF Albert Sambi Lokonga, 4 -- Lokonga picked up the ball in deep positions but was slow in transitioning the ball. He was also guilty of losing possession on numerous occasions.
MF Granit Xhaka, 5 -- Was allowed to venture further forward in the second half and it almost paid off when his effort was well saved by Forster.
FW Bukayo Saka, 6 -- The winger should have given Arsenal the lead when he had the goal at his mercy, but his effort -- with his weaker foot -- was tipped over the bar by Forster. He came close twice in the second half but just couldn't get the better of Forster.
FW Eddie Nketiah, 6 -- Led the line in Alexandre Lacazette's absence and worked tirelessly to put pressure on the Southampton defence. He had to be patient for his first effort on goal, however, but like his teammates couldn't find a way past Forster.
FW Gabriel Martinelli, 6 -- Had Arsenal's first chance of the game. He cut in from the right side onto his left foot and forced Forster into a save low to his right. He then set up Saka with an excellent pass shortly afterwards. Looked bright throughout.
Emile Smith Rowe (Soares, 60) 6 -- Brought a greater sense of urgency to Arsenal's attack, which will leave fans scratching their heads as to why he didn't start.
Nicolas Pepe (Tavares, 70) N/A -- The Frenchman looked lively in the last 20 minutes. Southampton will be grateful he didn't start the game.