Watford on Sunday announced Xisco had "left his post" at the club as the Spaniard became the first manager to be sacked during the new Premier League season.
Xisco, 41, arrived at Vicarage Road in December 2020 and guided the club to promotion to the Premier League. Watford started their return to the top-flight with an opening day 3-2 win over Aston Villa but have since suffered four defeats in their next six matches.
Xisco's last match in charge was the 1-0 defeat at Elland Road, which earned Leeds United their first win of the season and dropped Watford to 14th in the table.
"Watford FC confirms Xisco Muñoz has left his post as the club's Head Coach," the club said in a statement.
"The Board feels recent performances strongly indicate a negative trend at a time when team cohesion should be visibly improving.
"The Hornets will always be grateful to Xisco for the part he played in securing last season's promotion and wish him well for his future career in football."
Xisco's departure continues a revolving-door policy at Watford dating back to 2008. Over the past 13 years, Watford have hired and fired 17 permanent managers.