The Spaniard took charge in May but was rarely popular with fans and results have been mixed with only 26 goals scored amid seven wins, five draws and ten defeats.
The 58-year-old, whose previous roles included Real Madrid, Spain and, in England, Wolves, leaves the Hammers 14th in the Premier League table with 23 points, seven above the relegation zone.
His replacement will inherit a team whose problems in front of goal have been exacerbated by the loss of Jarrod Bowen with a broken foot and Michail Antonio to injuries following a car crash. Summer signing Niclas Füllkrug has only scored twice, his form hindered by injuries and a style unsuited to Lopetegui's tactics.
Potter, who was successful at Brighton before a difficult seven-month spell at Chelsea, is reported to have been in talks with West Ham for several days, though Lopetegui's departure was not confirmed until Wednesday afternoon.
A club statement said: "West Ham United can confirm that head coach Julen Lopetegui has today left the club.
"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 London club are the fifth in the 20-club Premier League to change their coach during this season following Manchester United, Leicester City, Wolves and Southampton.
Potter will bring the number of Englishman managing in the Premier League to three, joining Eddie Howe (Newcastle) and Sean Dyche, though the latter is under pressure at Everton.
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