The former Bournemouth and Burnley boss announced in a statement on Newcastle's website that it was 'the right time' to step away from a club where he had brought success.
Howe ended the Magpies' trophy drought in 2024, winning the League Cup, their first success in 70 years, whilst also bringing Champions League football back to St James' Park.
His coaching staff, Jason Tindall, Graeme Jones, Stephen Purches and Simon Weatherstone, and head of performance Dan Hodges, have also departed.
In the lengthy statement, Howe said: “After nearly five years of giving my life, heart and soul into the club with unrelenting energy, I feel that it is in the best interests of both myself and the club to step away, recharge and take a break.
“Although it’s been incredibly difficult to make this decision, I know in my heart that it’s the right one. I have always put the best interests of Newcastle before my own in every single decision I have made whilst I’ve been here and this one is no different.
“It has been the privilege of my lifetime to have been the manager of Newcastle United."
Read more analysis on Howe's departure here.
David Hopkinson, Newcastle United’s CEO, added: “Eddie and his staff leave with the deep gratitude and respect of everyone at Newcastle United, and with a lasting place in the club’s history.
“While we are naturally disappointed to see Eddie leave, we remain immensely thankful for everything he has done for the club.
“On behalf of our owners, Board, players, staff and supporters, I would like to extend sincere thanks to Eddie for his outstanding service and leadership, and wish him and his family every success and happiness for the future.”
The Magpies also said that they are in advanced stages of finding Howe's replacement, with reports all but confirming that it will be Al Ahli manager Matthias Jaissle. The 38-year-old has won the Asian Champions League with the Saudi club, who, like Newcastle, are run by the country's Private Investment Fund (PIF).
Newcastle begin their season against Liverpool on August 23rd.