The 42-year-old returned to the club in the summer after departing for Wealdstone in January, where he lasted just 73 days.
His second coming at St Albans didn’t have a happy ending either and with just two league wins all season, the club find themselves in the bottom four of the National League South.
Now they begin the hunt for a manager to steer the club to survival.
Director of Football Harry Wheeler will take charge of the team for this weekend’s match against Chippenham Town at Clarence Park.
Lawrence Levy, a member of the Saints’ Senior Leadership Team, said: “I want to thank David for the considerable contribution he has made to this club as a player, manager and coach.
“ As a player, he was key to our FA Cup run and victory over Forest Green Rovers in front of a sell-out crowd at The Park in 2021.
“When former manager, Ian Allinson, left the club David took over the role of manager at short notice and led the club into the play-offs, taking us to the National League South Promotion Final.
“I will always be thankful to David for his tireless effort to achieve success for this football club. David is a very talented coach and well respected in football but also someone I consider to be a friend. Everyone at the club wishes him the very best for the future.”
The search for Nobel’s replacement for a new manager will begin immediately and Levy said: “The club is focused on the recruitment process, and we will be updating supporters in the near future on this.
“In the meantime, we hope that fans will come along on Saturday, to show their support and get behind Harry and the team.”