Who defeat Manchester United the most? Arsenal have also defeated Manchester United in league competition on 74 occasions, which represents the most Manchester United have lost against any club. Manchester United’s Premier League supremacy can be traced back to Sir Alex Ferguson’s tenure at the club. Manchester United was regarded as the most hated team in the division during Ferguson’s tenure, owing to their ability to easily defeat opponents. Through their remarkable dominance, Manchester United has struggled to reign supreme over one team since the Premier League’s inception in 1992. Manchester United’s biggest rival is still Chelsea. Chelsea is an outlier, as Manchester United has beaten and outscored Liverpool, Arsenal, and Manchester City in their head-to-head matches. The only team that has a better head-to-head record than Manchester United is Chelsea. In addition, they are the only team in Premier League history to have defeated Manchester United the most times.