Sao Paulo sacked coach Adilson Batista in the changing rooms right after Sunday's 3-0 defeat at Atletico Goianiense, their sixth match without a win.
It was the 31st coaching change of the year among Brazil's 20 first division clubs.
"We talked during the week that this match with Atletico was of utmost importance for the [coach's] permanence, or not, and continuing the job," Sao Paulo's director of football Adalberto Batista said.
"Sadly, today we had another adverse result, added to the others, the pressure... the work ends today," he told reporters at the Serra stadium.
"In football the result is what matters and in our last six matches we got four points."
Sao Paulo have dropped from second to sixth in the Brazilian championship standings, six points adrift of arch-rivals and leaders Corinthians with eight matches to go.
Adilson took charge at Sao Paulo in July and presided over 22 matches in all competitions with seven wins and six defeats.
Assistant Milton Cruz will takes charge as caretaker for the remainder of the championship and the Copa Sudamericana, the club said on their website.
Corinthians, Coritiba, Flamengo and Palmeiras are the only first division clubs to have avoided changing coaches this year. At the other end, struggling Atletico Paranaense are on to their fifth coach.
The defeat at mid-table Goianiense was even worse for Sao Paulo on a weekend when the five other leading teams all won and are separated by a mere four points in the closest title race since the present league format was introduced in 2003.
Corinthians beat relegation-threatened Cruzeiro 1-0 away at the Alligators' Arena after the home team's Argentine midfielder Walter Montillo hit a second-half penalty over the bar missing the chance to equalise.
Cruzeiro's arch-rivals Atletico Mineiro, also fighting to avoid the drop, conceded two goals in 18 minutes to go down 2-0 at Vasco da Gama, while Botafogo beat Atletico Paranaense at home by the same score.
After 30 matches, Corinthians and Vasco are level on 54 points with Botafogo on 53 and a game in hand, Flamengo 51 and title holders Fluminense 50.
On Saturday, Fluminense beat Palmeiras 2-1 away with two goals from Brazil striker Fred, while Flamengo beat Ceara 1-0 despite having captain Ronaldinho sent off in the second half for dissent.comments