Slade only took over at the Ricoh Arena in December, but equalled an unwanted club record by failing to win any of his first nine league matches at the helm.
Victory over Gillingham last month saw him end that winless run at the 10th attempt, but it proved to be his only league triumph at the club, with subsequent defeats to fellow strugglers Swindon Town and Bury seeing the Sky Blues drop to the foot of the table.
Slade did help Coventry to the final of the EFL Trophy, but he will not be in charge for the Wembley showpiece after Saturday's 0-0 draw away to Shrewsbury proved to be his last game in charge.
"Coventry City FC has today parted company with first-team manager Russell Slade, effective immediately," read a short statement from the club.
"The club would like to wish Russell all the very best for the future. A further announcement will follow in due course."
Coventry, whose next match comes at home to Bradford on Saturday, are currently 13 points from safety in League One.