The former Real Madrid and Spain boss took charge of Wolves last November with the club bottom of the Premier League table and guided them to 13th place at the end of the season.
Lopetegui was hoping to help Wolves kick on this season but a lack of funds have made it difficult for him to bring in his preferred transfer targets.
Ruben Neves has been sold to Al Hilal while Raul Jimenez has joined Fulham.
Matt Doherty's return to Molineux as a free agent is the only notable incoming at Wolves this summer.
A club statement announcing Lopetegui's departure from Wolves read: "The head coach and club acknowledged and accepted their differences of opinion on certain issues and agreed that an amicable end to his contract was the best solution for all parties."
Speaking to the club's official website, Lopetegui said: "I wish Wolves and everybody at the club the very best of luck for the future, and thank them for the opportunity granted at the time to take charge of this wonderful club. It has been an honour to enjoy this adventure in the day-to-day company of Matt Hobbs, Matt Wild, head of player care Lisa Hollis and every single employee of the club; whom I wish to thank for their support and help at every moment.
"Also, of course, I want to thank the players, who have always given the maximum to achieve our objectives, and especially the fans that made me feel like one of them from the very first moment and have always been amazing to me, my staff and my family."
Former Bournemouth manager Gary O'Neil is favourite to replace Lopetegui.
Wolves play their first Premier League game away at Manchester United on Monday.