West Ham lost 4-1 to Manchester City on the weekend after being thumped 5-0 by Liverpool before the new year. The Basque leaves the Hammers in 14th place, seven points above the relegation zone.
"West Ham United can confirm that Head Coach Julen Lopetegui has today left the Club," the Premier League side announced in a statement.
"The first half of the 2024/25 season has not aligned with the Club’s ambitions and the Club has therefore taken action in line with its objectives.
"The Club can confirm that Assistant Head Coach Pablo Sanz, Head of Performance Oscar Caro, Head Analyst Juan Vicente Peinado, Fitness Coach Borja De Alba and Technical Coach Edu Rubio have also left with immediate effect.
"The Board would like to thank Julen and his staff for their hard work during their time with the Hammers and wish them every success for the future," the official statement continued.
Lopetegui took over at West Ham in May, agreeing on an initial two-year deal to replace the outgoing David Moyes.
Already knocked out of the EFL Cup by Liverpool, the Hammers have claimed just six wins in the Premier League this season.
No replacement has been confirmed but former Chelsea and Brighton boss Graham Potter is heavily linked with the role and is expected to be announced as the club's new manager.
West Ham's next Premier League match is against ninth-placed Fulham at home on Tuesday the 14th. They face Aston Villa in the third round of the FA Cup this Friday (10th).