Los Pepineros have collected just two points from their opening nine games and are currently seven points adrift of 17th-placed Celta Vigo in the league.
The former Southampton, Alaves and Valencia manager was appointed at the start of last season and guided Leganes to survival and a respectable 13th in La Liga.
But results took a turn for the worse at the beginning of this campaign and the club issued a statement on Monday on the Argentine’s future.
"Leganes and Mauricio Pellegrino have decided mutually to go their separate ways," the statement read.
"The Argentine coach, who last year led the team to secure its status in the top flight, will not be in charge of the team for next week's game against Mallorca.
"Reserve team coach Luis Cembranos and his assistant Carlos Martinez will take charge of the team for the next few training sessions."