The Minstermen lost 1-0 at Curzon Ashton this afternoon as their poor season continued.
It left the club in 15th position in the National League North.
Defeat at Thameside on Saturday was York’s third loss in four matches.
Collins only officially took over in October after being handed the job on a full-time basis when Martin Gray was sacked.
“Sam Collins has left his role as manager of York City Football Club with immediate effect,” said the club tonight.
“Sporting Director Dave Penney will oversee training until a new manager is appointed.
“The club's board would like to thank Sam for his hard work and professionalism.”