Despite leading the Rams to an exciting Carling Cup semi-final tie against Manchester United, their 1-0 home defeat against Ipswich Town was the last straw for Jewell.
Derby County are currently 18th in the Championship and chairman Adam Pearson expected this resignation as Derby County are in danger of slipping down another division.
"It was probably one result too far for Paul," said Pearson. "He came to see me after the game and said that he felt it just wasn't working out and didn't want to club to suffer as a result.
"He just feels that the club needs a fresh impetus and a new direction.