Welshman Hughes, 47, was appointed Newport boss in May, stepping down as a youth coach at Manchester United in order to take his first senior managerial role.
But he has endured a miserable spell at Rodney Parade, with Newport’s inexperienced squad struggling to deliver results amid fan criticism of chairman Huw Jenkins’ recruitment policy.
Newport had hoped for progress in 2025-26, having finished the last campaign in 22nd, with head coach Nelson Jardim leaving the club in April after just under a season in charge.
They began the new campaign with signs of promise, beating Barnet on penalties in the Carabao Cup and then taking four points from Hughes’ first two league games.
However, they have lost their past seven home league matches and their 1-0 defeat at fellow strugglers Shrewsbury Town proved to be Hughes’ final game in charge.
His exit leaves Newport looking for a fifth permanent boss since Mike Flynn departed in 2021.