Southampton, the last-place club in the Premier League, fired manager Russell Martin after an embarrassing 5-0 home defeat to Tottenham on Sunday.
The club said in a statement it had taken the "difficult decision to part ways" with Martin after just one win in 16 games.
Southampton, promoted last season, is rooted to the bottom of the table, nine points from safety.
"We can confirm that we have taken the difficult decision to part ways with our men's first team manager Russell Martin," the club said.
"Going into the start of the season, we all knew the challenges that we would face this year as we readjusted to life in the top flight, competing in the best and most competitive league in the world.
"However, the reality of our situation is clear. The board have supported Russell and his staff and been open and transparent regarding our expectations. We have all been on the same page in recognising the urgency of needing results to improve."
Current Under-21s boss Simon Rusk will take charge of the team on an interim basis until a permanent replacement is announced.
Southampton conceded five first-half goals against Tottenham on Sunday evening.
"I was hurt in the first half," Martin said after the match. "We did not respond very well to the setbacks as a group.
"We have seen that all too often this season. After the first goal, our response was very poor."
Speaking about his future, the 38-year-old former Scotland international said: "We have no choice but to keep working and fighting. It's what I have been doing in this job and I will continue doing it until I am told not to."