Tisdale has spent the last 12 years at the Grecians - making him the longest-serving boss in the Football League - but an exit became a possibility as the 45-year-old failed to agree a new deal.
Exeter continued to hold discussions with Tisdale - who also represented the club during his playing career - but it has now been revealed that the 45-year-old has made his exit after 626 matches in charge.
Chairman Julian Tagg told the club's official website: "We wish him the best of luck for the future and would like to thank him for his commitment to our club over the last 12 years.
"He has been a dedicated and successful manager, well respected both inside the club and equally so in football generally and ever popular with players staff and volunteers, having worked so extremely hard to bring Exeter City to where we are today.
"Our offer of a new contract to Paul came with our express desire that he sign it in order to allow the club to plan and go forward with certainty. It is of course entirely Paul's prerogative that he should choose to let the club's deadline for a decision pass, but we are now at the point where we must move on and unexpectedly plan for a future without Paul as our manager."
Earlier this week, Exeter suffered defeat in the League Two playoff final, losing 3-1 to Coventry City.