Mkhitaryan made his debut in a 2–0 victory in a pre-season match against Wigan Athletic on 15 July 2016. On 7 August 2016, he made his competitive debut as a stoppage-time substitute in a 2–1 victory against Leicester City in the 2016 FA Community Shield. He became the first Armenian to play in the Premier League on 14 August 2016 when he came on as a 75th-minute substitute for Juan Mata in a 3–1 away victory against Bournemouth. He made his first Premier League start for Manchester United in the Manchester derby on 10 September 2016, but he was substituted at half-time.