FA Cup holders Arsenal were knocked out of the competition after a Gabriel Magalhaes own goal gave Southampton the edge in a scrappy game.
Gabriel turned a cross-shot from Kyle Walker-Peters for the only goal.
Southampton dumped FA Cup holders Arsenal out of the competition on Saturday, winning 1-0 courtesy of a Gabriel own goal to set up a fifth-round meeting with Wolves.
The much-changed Gunners, who have won the competition a record 14 times, fell behind midway through the first half and could not find a way back.
Mikel Arteta made seven changes from their 3-0 Premier League win against Newcastle on Monday.
Southampton, who had never previously beaten Arsenal in the FA Cup, were the brighter team in the first half in the winter sunshine on England’s south coast.