Smith, previously head of academy coaching, joined the Spireites two years ago while former academy boss Gerry Carr left the Proact Stadium last Friday by mutual agreement.
Chesterfield chief executive Chris Turner said: “It is a natural progression for Mark, who has a wealth of experience in the game, and I believe it is a major step forward for youth development at the club.
“The improvement in the quality of the youth team is there for all to see, as highlighted by the fact that Laurence Maguire and Jake Beesley were both handed professional contracts at the end of last season.”
Smith added: “I am delighted to have been given this opportunity. I really enjoy working at the club and I am passionate about the development of young players so it is a challenge that really excites me.”