Marcelino has been sacked as Valencia coach after an indifferent start to the season, the Spanish La Liga club said on Wednesday.
The 54-year-old, who won the Copa del Rey and secured Champions League football last season, leaves after two campaigns at the helm.
"Valencia told Marcelino Garcia Toral on Wednesday that he is no longer first team coach," a club statement said.
"The club would like to thank him for his work and dedication during his time at our entity and wish him success for the future."
The departure had been mooted in what turned out to be a tumultuous pre-season for the club, with local media reporting the coach was not happy with owner Peter Lim over transfer policy.
It appeared that the differences had been resolved. However, after taking four points from their opening three games, they have taken the decision to replace Marcelino.
Reports across the country suggest former Spain Under-21 head coach and ex-Real Madrid assistant Albert Celades will be appointed later on Wednesday.
The upheaval comes at a crucial time for Valencia, who travel to La Liga champions Barcelona on Saturday, before visiting Chelsea in their opening Champions League group game next week.