The visitors didn't take long to open the scoring as Christian Eriksen cut through Sheriff's midfield to find Jadon Sancho, whose finish was impressive after cutting back onto his left foot.
Sancho then almost doubled his tally with a placed effort that was cleared off the line by Stjepan Radeljic, but Man United soon went two goals to the good after Diogo Dalot won a penalty that Cristiano Ronaldo smashed down the middle to beat the goalkeeper.
The Red Devils looked content to keep possession after the restart, as they maintained their control of the match. Bruno Fernandes came close with a first-time strike from Dalot's cross, and while Sheriff tried to respond, the hosts lacked conviction when looking to execute their final touch.
An assured win from the Premier League side saw them show their class with a professional performance. Manchester United were patient in possession, and it looked as though all three parts of their system were working cohesively. A deserved three points.
Erik ten Hag's side could have been more clinical in the second half, though it might be harsh to consider that a negative.
Manager rating (out of 10)
Erik ten Hag, 7 -- A positive team selection from Ten Hag showed his intentions to take the Europa League seriously, while his system provided an optimal balance between maintaining control of the game and creating high-value chances without committing too many players forward.
Player ratings (1-10; 10 = best, players introduced after 70 minutes get no rating)
GK David De Gea, 6 -- There wasn't a great deal for De Gea to do across the game, with Sheriff's best chance a long-range effort in the first half when Iyayi Atiemwen made space.
DF Lisandro Martínez, 7 -- Passed the ball out of defence impressively and was quick to stop counter-attacks with his pace. Made a number of clearances to allow his team to get back into defensive shape.
DF Raphaël Varane, 7 -- Alert to the danger and dealt with developing situations by anticipating them quickly. Varane was also calm on the ball and looked to take his opportunities to transition forward quickly.
DF Tyrell Malacia, 6 -- Malacia kept things relatively simple over an overall solid performance. The 23-year-old could have been a little bit more careful in the first half with fouls he gave away, but he rarely looked troubled defensively.
DF Diogo Dalot, 7 -- Dalot used any opportunity to get forward that he could and proved difficult to pick up by the home side, winning a penalty for Manchester United in the 39th minute. Unlucky not to pick up an assist with his low cross that found Fernandes.
MF Bruno Fernandes, 7 -- A strong performance and rarely made a wrong decision on the night. The 28-year-old was always an option from the number 10 role, and he showed positive link-up play when getting the ball to Manchester United's wingers. Should have done better with his effort just after the restart.
MF Christian Eriksen, 8 -- The Denmark international was able to progress the ball into promising areas with his vision finding players in space. He picked up the assist for Sancho's goal with a pass that cut through Sheriff's midfield with ease, and that set the tone for his overall game as he continued to dictate the play from the middle of the pitch.
MF Scott McTominay, 7 -- Yet another dominant display from the midfielder saw him recover possession for his side time and time again in the 45 minutes he starred in on the night. Replaced at the break by Casemiro.
MF Antony, 6 -- Antony had some positive moments but he drifted in and out of the game too much overall. A direct pass in the first half almost helped him to an assist but Ronaldo's angle to the goal was narrow.
MF Jadon Sancho, 7 -- Sancho looked dangerous when in possession and cut back majestically onto his left foot before striking Manchester United into the lead. Came close to scoring a second that was cleared off the line.
FW Cristiano Ronaldo, 6 -- Ronaldo's strike from the spot secured his 699th club goal across his career. While he looked frustrated in some moments, his movement consistently caused problems for the home side.
Casemiro (McTominay, 45"), 7 -- Introduced at half-time, Casemiro impressed with his passing from midfield, with the former Real Madrid midfielder not afraid to attempt direct balls into dangerous areas. Some strong defensive stops helped win back possession for his side.
Luke Shaw (Dalot, 70"), N/R -- Useful minutes for Shaw who came on and didn't need to play with much intensity from left-back.
Anthony Elanga (Ronaldo, 81"), N/R -- Caused problems inside the box when brought on for Ronaldo.
Alejandro Garnacho (Antony, 90") N/R -- An appearance for 18-year-old Argentina international Garnacho late-on.
Harry Maguire (Martinez, 90") N/R -- Replaced Martinez for the two minutes of stoppage time.