Derek Martin, who has played Slater stalwart Charlie for a decade, will bow out later this year, while Cliff Parisi's role as unlucky-in-love mechanic Minty Peterson will also come to an end after eight years under new producer Bryan Kirkwood.
Relative soap newcomer Liam Bergin's exit storyline is currently being penned as his alter ego Danny Mitchell's scheming ways are expected to reach a climax over the following months.
Speaking of his departure, Bergin said: "I've had a great six months working on EastEnders playing Danny. He has been a great character to play and without giving too much away, he's sure to ruffle a few feathers before he leaves Walford."
He continued: "Working alongside Barbara [Windsor], Sam [Womack], Rita [Simons] and Steve [McFadden] has been a real pleasure and I will enjoy watching what the Mitchells get up to as a viewer."
Meanwhile, Owen Turner's mother Liz - played by Kate Williams - will also film her final scenes later this year and is expected to depart in a storyline connected with her son Owen's murderer Lucas.
David Proud, who became EastEnders' first ever disabled character in June, will further be written out.
Of his time filming with the serial, Proud said: "I have had a wonderful time at EastEnders and loved every minute of it over the last year. It has been fantastic to play such a complex character like Adam. I have made some great friends amongst the cast and crew and wish the show all the best for future."
At the beginning of the month, Chelsea Fox actress Tiana Benjamin revealed her intention to leave after four years in a bid to pursue other projects. Preeya Kalidas will make her screen exit in a fortnight's time, while Barbara Windsor is due to film her final scenes as matriarch Peggy Mitchell in July.
A show insider told DS: "It's sad to see characters leave the Square but obviously when a new executive producer like Bryan Kirkwood comes on board, they're always keen to refresh the show and make some changes."
They added: "It's the way soaps work - characters run their course and new characters come along."
Since his arrival, Kirkwood successfully managed to lure back Jessie Wallace and Shane Richie as Kat and Alfie Moon, while also casting former Footballers' Wives actress Zöe Lucker as Max Branning's new love interest Vanessa.