Speculation is mounting he could be set to return to Hull City where he enjoyed success as chairman before moving to Derby two years ago.
Pearson took over as chairman at Pride Park in October 2007 after buying the majority shareholding from Peter Gadsby.
However, in his first season at the helm Derby suffered relegation from the Premier League and the Rams have been unable to win promotion back to the top flight.
Derby have endured a difficult start to the season with the club currently languishing in 19th spot in the table just four points clear of the bottom three.
The Rams are understood to have financial problems with the club looking to trim the squad and reduce their wage bill in a bid to save finances.
Pearson will be replaced by Tom Glick, who is the club's chief executive and
Pearson has cited the need to pursue "new challenges" as a key reason behind his decision to quit the club coming up to the second anniversary of his arrival at Pride Park.
"Surprising as it may seem, I have thoroughly enjoyed the two years I have spent at Derby County, despite not achieving the playing success on the pitch we had all hoped for and worked so hard for in that time," Pearson told the club's official website.
"It has been an absolute pleasure and privilege to work with Nigel Clough over the past ten months. He is a manager in whom the supporters and Board can totally trust with the future of their club.
"I have no doubt at all that Nigel, supported by his staff, will go on to be a truly great manager for this football club and create his own legacy, in the footsteps of his father.
"Under Nigel Clough's management the wage bill is now under control, the squad size is under control, the Academy structure is solid and we have a management team in place who will take the team forward.
"I would like to thank Andy Appleby and the Board for all their support over the last two years and also the rest of the investor group who have been so supportive and enthusiastic towards myself and the club.
"I would like to thank all the staff at Moor Farm and Pride Park for their support and help over the past two years; they are a very talented, dedicated group, who will get the success their efforts deserve.
"I wish the directors, management, players, staff and most of all the supporters the very best and success for the future."