Setchell has been in charge since September 2017, leading Wisbech to promotion from the United Counties League Premier Division.
He said: “I know it’s a cliché, but I feel as though I’ve taken the club as far as I can. With my work commitments, the travelling – which is still significant next season – and the finances, there were a number of hurdles in the way to me continuing as manager and the combination of those factors has led me to take this difficult decision.
“I do, of course, wish the club the very best for the future and hope that they can consolidate at Step 4 in the years to come.”
Wisbech ended up finishing 17th in their first season in the EVO-STIK League East Division.
Chairman Paul Brenchley said: “I’d like to personally thank Gary for his time with the club. He did a great job and myself and the other Directors now have the unenviable task of filling the void which he has left.
“I understand that Gary’s backroom staff of Darren Edey and Luke Hipwell are also leaving the club and we thank them for their efforts.”