The 38-year-old oversaw Wakefield's relegation from Super League this year after winning just four games in challenging circumstances in his only season in charge at Belle Vue.
New owner Matt Ellis last month outlined his intention to appoint former Castleford Tigers and Warrington Wolves boss Daryl Powell on a four-year contract once his takeover was ratified.
Powell will be tasked with leading Trinity back to the top flight following an ill-fated campaign.
Wakefield came into 2023 with a small squad and suffered a catalogue of injuries throughout the year to leave Applegarth with an improbable task.
Applegarth played 47 times for his hometown club before returning as a coach in 2016 and working his way through the ranks, including a successful five-year spell as head of youth.
The former forward is seeking a fresh challenge after deciding against exploring the opportunity to stay on at Belle Vue in another capacity.
"Firstly I’d like to thank Michael (Carter, chief executive) and the board for the opportunity to lead this great club and the support they have shown me, not only this year but since I first came back in 2016," said Applegarth.
"It’s been a privilege and an honour to coach my hometown club. Whilst it was disappointing for it to finish as it has under challenging circumstances, the opportunity doesn’t come round often.
"I gave it everything I had with every decision made with the best interests of the club at heart.
"I genuinely wish Matt, Daryl and the rest of the new team well. It's an exciting time to be supporting Wakefield and after speaking with Matt on numerous occasions, I know he has a burning desire to take this club back to where it belongs which is challenging for honours on a regular basis."
Former Featherstone Rovers boss Sean Long, who linked up with Wakefield in August as Applegarth's right-hand man, has also left the club.
Carter has hailed Applegarth's contribution to Trinity during his long stint on the coaching staff.
"I’ve spoke to Mark at length regarding his role at the club with the imminent takeover and Mark has decided to seek pastures new," said Carter.
"When Mark joined the club back in 2016, he managed to turn a failing academy into one that has consistently produced players and being assessed as Good and in some parts Excellent by the RFL. This was no mean achievement given the shoestring budget he was operating with.
"Then when given the chance to become head coach, despite the numerous challenges – financial and otherwise – he gave it his all, and his work ethic for this club can only be admired.
"Mark has given his heart and soul to this club and will be sorely missed. I wish him and his family every success for the future, and he is welcome back at any time."