Cristiano Ronaldo ended his barren spell with the first Europa League goal of his career as Manchester United earned victory at Sheriff Tiraspol.
Erik ten Hag's men suffered defeat at Old Trafford in their Group E opener against Real Sociedad but responded by claiming all three points in Moldova.
The Red Devils opened the scoring in the first half as a lovely team move was coolly finished off by Jadon Sancho from Christian Eriksen's reverse pass.
Sancho, who was left out of the England squad earlier in the day, came close to a second but his low shot was brilliantly cleared off the line by Sheriff captain Stjepan Radeljic on the stretch.
But United did double their advantage before half-time courtesy of Ronaldo's penalty, awarded after Patrick Kpozo tripped Diogo Dalot in the box.
Ronaldo could have taken his tally to 700 club goals but side-footed over from the edge of the area while at the other end, Sheriff could not force David de Gea into any meaningful saves.
In the group's other game, Real Sociedad made it two wins from two with a 2-1 victory over Neil Lennon's Omonia Nicosia.
Sancho sends Southgate a reminder
United's revival following a poor start to the season was brought to a halt at home by Real Sociedad last week, but the side got back to winning ways with a professional job against Sheriff.
Portuguese star Ronaldo played a key part in the triumph, having requested to leave Old Trafford during the transfer window for Champions League football, but ending up staying as no club came in for his services.
The 37-year-old had not scored in his previous eight games for United, a run stretching back to the end of last season, but he showed signs of ending that goal drought when he blazed over from an angle.
He did get off the mark of the campaign by slotting in a spot-kick - which was the 699th club goal of his career - but will not get the chance add to that until 2 October against rivals Manchester City, as Sunday's scheduled Premier League against Leeds has been postponed.
Ten Hag's squad will then be tested to its limits after the international break with a gruelling period of 13 games in the space of 43 days before the season stops in November for the Qatar World Cup.
The visitors started slowly in the Moldovan capital of Chisinau, the match being played there for security reasons, but netted with their first real attack of the contest.
Winger Sancho has been in good form recently but failed to make the Three Lions squad for the forthcoming Nations League matches against Italy and Germany and his World Cup place is now in serious doubt.
But he sent manager Gareth Southgate a reminder of his capabilities by turning a defender and calmly converting his third goal of the season and should have had another but for Radeljic's last gasp interception.
United were in control of the contest but could not add to their tally in the second half, with captain Bruno Fernandes' first-time strike straight at goalkeeper Maksym Koval.
Sheriff unable to repeat past heroics
Sheriff caused one of the biggest shocks in European football history last season when they defeated eventual winners Real Madrid in the Champions League group stage.
Many of that squad have now departed, including manager Yuriy Vernydub, who left the club earlier this year to join Ukraine's territorial defence following February's invasion by Russia.
The side are six points clear at the top of the table in their domestic league but their challenge petered out after a bright start against United, with Cedric Badolo's long range effort and well struck free-kick straight at De Gea.
Iyayi Atiemwen twice came close, a strike from range bouncing just wide as well as curling a free-kick narrowly over.
Player of the match
EriksenChristian Eriksen
Sheriff Tiraspol
Squad number28Player namePernambuco
Squad number18Player nameKyabou
Squad number17Player nameMudasiru
Squad number11Player nameFelipe Vizeu
Squad number2Player nameKpozo
Squad number15Player nameKiki
Squad number7Player nameOuattara
Squad number35Player nameKoval
Squad number10Player nameBadolo
Squad number6Player nameRadeljic
Squad number61Player nameAkanbi
Squad number20Player nameZohouri
Squad number8Player nameDiop
Squad number80Player nameAtiemwen
Line-ups
Sheriff Tiraspol
Formation 4-3-3
35Koval
20Zohouri15Kiki6Radeljic2Kpozo
8Diop18Kyabou10Badolo
7Ouattara80Atiemwen61Akanbi
35Koval20Zohouri15Kiki6Radeljic2KpozoBooked at 38mins8Diop18Kyabou10Badolo7OuattaraSubstituted forRodrigues da Silva dos Santosat 73'minutes80AtiemwenBooked at 63minsSubstituted forMudasiruat 81'minutes61AkanbiSubstituted fordos Reis Pereira Vizeu Do Carmoat 73'minutesSubstitutes
1Celeadnic4Crespo da Silva11dos Reis Pereira Vizeu Do Carmo12Moumouni17Mudasiru28Rodrigues da Silva dos Santos33Pascenco42Guedes BorgesMan Utd
Formation 4-2-3-1
1de Gea
20Dalot19Varane6Martínez12Malacia
39McTominay14Eriksen
21dos Santos8Bruno Fernandes25Sancho
7Cristiano Ronaldo
1de Gea20DalotSubstituted forShawat 70'minutes19Varane6MartínezSubstituted forMaguireat 90'minutes12Malacia39McTominaySubstituted forCasemiroat 45'minutes14Eriksen21dos SantosSubstituted forGarnachoat 90'minutes8Bruno Fernandes25Sancho7Cristiano RonaldoSubstituted forElangaat 81'minutesSubstitutes
2Lindelöf5Maguire17Fred18Casemiro22Heaton23Shaw36Elanga49Garnacho50Vítek55Iqbal56McNeillLive Text
Match ends, Sheriff Tiraspol 0, Manchester United 2.
Second Half ends, Sheriff Tiraspol 0, Manchester United 2.
Substitution, Manchester United. Harry Maguire replaces Lisandro Martínez.
Substitution, Manchester United. Alejandro Garnacho replaces Antony.
Attempt missed. Patrick Kpozo (Sheriff Tiraspol) left footed shot from outside the box is too high.
Attempt saved. Pernambuco (Sheriff Tiraspol) left footed shot from outside the box is saved in the centre of the goal.
Foul by Casemiro (Manchester United).
Stjepan Radeljic (Sheriff Tiraspol) wins a free kick in the attacking half.
Foul by Casemiro (Manchester United).
Salifu Mudasiru (Sheriff Tiraspol) wins a free kick in the attacking half.
Foul by Luke Shaw (Manchester United).
Pernambuco (Sheriff Tiraspol) wins a free kick on the right wing.
Hand ball by Anthony Elanga (Manchester United).
Corner, Manchester United. Conceded by Armel Zohouri.
Substitution, Manchester United. Anthony Elanga replaces Cristiano Ronaldo.
Substitution, Sheriff Tiraspol. Salifu Mudasiru replaces Iyayi Atiemwen.
Cristiano Ronaldo (Manchester United) wins a free kick in the defensive half.
Foul by Gaby Kiki (Sheriff Tiraspol).
Casemiro (Manchester United) wins a free kick in the defensive half.
Foul by Iyayi Atiemwen (Sheriff Tiraspol).