After a strong finish to last season under Hughes, expectations were high at the Racecourse Ground for the coming season.
But with the club winless in eight games, the ex-Hull and Birmingham City midfielder has left the club.
It comes after a statement two days ago in which Hughes expressed his desire to turn things around.
Tuesday night's loss to AFC Fylde, in which the Dragons twice led, proved to be his last game in charge.
A club statement reads: "Following on from our previous statement, Wrexham AFC can confirm that further discussions between Bryan Hughes and the board have taken place and following those discussions all parties decided that a change was needed.
"The outcome is that Bryan has left his position of First Team Manager with immediate effect.
"We would like to thank Bryan for his hard work, effort and for acting in the best interests of Wrexham AFC at all times during his time at the club."
The club have not yet made an announcement on Hughes' replacement.