Following the departure of Louis van Gaal at the end of the previous season, the club signed former Porto, Chelsea, Inter Milan and Real Madrid manager José Mourinho on a three-year contract, with the option of a further year.

[14] United cruised to a 4–0 victory on 7 January with first-half goals from Wayne Rooney – who equalled Bobby Charlton's 249-goal record for the club in the process, Anthony Martial and a second-half brace from Marcus Rashford.

In a fiercely contested game, Ander Herrera was sent off and N'Golo Kanté scored the winning goal to end Manchester United's defence of the FA Cup.

As one of seven English clubs who qualified for European competition in the 2015–16 season, United received a bye to the third round of the EFL Cup, the draw for which took place on 24 August 2016.

The match was played 21 September 2016 and Manchester United won 3–1; Michael Carrick opened the scoring in the 17th minute, but Northampton's Alex Revell equalised from the penalty spot shortly before half-time.

The draw for the fourth round took place shortly after the match and United were drawn at home against rivals Manchester City.

Manchester United's only previous meeting with Saint-Étienne came in the first round of the 1977–78 European Cup Winners' Cup; the second leg was played at Home Park in Plymouth after Manchester United were banned from playing within 200 kilometres (120 mi) of Old Trafford, following crowd trouble at the first leg in Saint-Étienne.

[16] The home tie saw Zlatan Ibrahimović score his maiden hat-trick for the club, while a goal from Henrikh Mkhitaryan in the second leg was enough to send United through.

United were drawn against Belgian side Anderlecht in the quarter-finals where Mkhitaryan scored in his fourth consecutive European away game.

United faced Dutch side Ajax in the final, with goals from Pogba and Mkhitaryan in either half leading them to victory for their first ever Europa League crown.