McTominay was associated with the Manchester United academy from the age of five after attending the club’s development centre in Preston. Having played as a centre forward in the earlier years of his youth career, McTominay converted to a central midfield role under Warren Joyce. He signed his first professional contract in July 2013.

On 30 April 2017, McTominay was named on the substitutes bench for a match against Swansea City in the Premier League. He made his first Premier League appearance on 7 May, coming on as a substitute against Arsenal, before starting Manchester United’s final Premier League match of the season on 21 May, a 2–0 win at home to Crystal Palace.

Ahead of the 2017–18 season, McTominay was named as a member of Manchester United’s touring party for their pre-season tour of the United States, as well as for matches against Vålerenga and Sampdoria. In the match against Vålerenga on 30 July 2017, McTominay came on as a substitute for Paul Pogba just after the hour mark, and 10 minutes later, he scored his first senior goal for the club – the third in a 3–0 win. McTominay made his first appearance of the season against Burton Albion in the EFL Cup on 20 September 2017, replacing Marcus Rashford in the 64th minute, in a 4–1 victory. He made his European debut on 18 October, against Benfica, coming on for Henrikh Mkhitaryan in injury-time, winning a free-kick and getting Luisão sent off before seeing out the 1–0 away win. Two days later, McTominay signed a new contract with United, keeping him at the club until June 2021, with an option to extend for a further year. He made his first start of the season on 24 October, in a 2–0 win over Swansea at Liberty Stadium in the EFL Cup fourth round.

McTominay was born in England but has Scottish ancestry through his father coming from Helensburgh. McTominay attended training camps with the Scottish youth sides. In November 2017, McTominay told Scottish Football Association performance director Malky Mackay that he wanted to concentrate on securing a place in the Manchester United first-team.

Speaking in February 2018, club manager José Mourinho suggested that new Scotland manager Alex McLeish should select McTominay “because it looks like England is missing him”. McTominay pledged his future to Scotland and was selected in their squad for two friendlies in March.

On 23 March, McTominay was one of four players to be given their international debuts in McLeish’s first game in charge. He played the first 57 minutes in a 1–0 friendly defeat to Costa Rica before being replaced by Stuart Armstrong. He made his first competitive appearance for Scotland in September 2018, as a 79th minute substitute for Callum McGregor in a 2–0 win against Albania.

On 21 January 2019, McTominay signed a contract extension, keeping him at United until 2023, with the option of another year. Replacing the injured Nemanja Matić, his first start of real significance under the management of Ole Gunnar Solskjær was against Liverpool on 24 February. McTominay was praised by pundits and reporters for his contributions in Champions League matches against Paris Saint-Germain and Barcelona. He scored his first competitive goal for United on 2 April 2019 in what was his 41st appearance for the club as they lost 2–1 to Wolverhampton Wanderers.

McTominay scored his first goal at Old Trafford in a 1–1 draw against Arsenal on 30 September 2019. On 27 October, McTominay scored United’s 2,000th Premier League goal in a 3–1 victory against Norwich City at Carrow Road. McTominay was credited with another goal, scored against Brighton on 10 November, after United successfully appealed to a Premier League panel that it should not be designated as an own goal by Davy Pröpper.

In November 2019 he was one of three Scotland players to withdraw from the national squad due to injury.

McTominay suffered a knee ligament injury on 26 December, which prevented him from playing for two months. He resumed full training on 19 February 2020. On 27 February, McTominay scored his first European goal in United’s UEFA Europa League Round of 32 second leg match against Club Brugge, with United winning 5–0 (6–1 on aggregate). On 8 March, he scored United’s second goal in a 2–0 win at home to Manchester City, shooting into an empty net from 40 yards after a mistake by goalkeeper Ederson, to help United to their first league double over their city rivals in a decade.

On 23 June 2020, McTominay signed a new contract with Manchester United set to keep him at the club until June 2025.

For the international games played in September 2020, McTominay was used as a centre-back in a three-man defence. The Times commented that McTominay had the physique needed for the position, but had struggled to adapt to the role. He continued in this role during the October 2020 internationals, and the Daily Record said that there were indications that his play had improved.