The former England boss was appointed by the Rams for a second spell in charge last October having previously been at the helm between 2013 and 2015.
He returned to the club after the departure of Nigel Pearson but has been unable to revive the Midlands side’s fortunes.
His final match in charge was Friday’s 3-0 defeat by title-chasing Brighton.
The club released a damning statement, claiming a “significant, unexpected and persistent decline in results, team unity and morale” had led to McClaren’s dismissal.
Derby have won one of their last nine league games and sit 10 points behind Sheffield Wednesday who occupy the final play-off spot.
Since the end of Nigel Clough’s reign in 2013, Derby have had four managers, none of whom have been able to take the club back to the Premier League.
Chairman Mel Morris said: “Steve is a great coach, we have very talented players and first class facilities but the heartbeat, commitment, focus and passion has been lacking something fundamental.
“The Brighton game on Friday night was so far from what we expect to see from those wearing a Derby County shirt.
“To ensure we are on the right path, it is important to put the building blocks in place so we can develop a team we can all be proud of. Players should wear the shirt with pride and share, espouse and exude the qualities and values we believe are important to the club, its supporters and the community.
“We need a manager who shares our values and who is prepared to develop the team, staff and processes that will set us on course for a sustainable place in the Premier League. We are less concerned about timescales than we are about getting things right. Of course we would like to achieve this sooner rather than later.
“That manager will of course be given the full support and backing of myself, the board, our executive team and staff to shape and develop the team around those who truly and demonstrably want to be part of Derby County.”