The Spain keeper had kept out efforts from Joaquin Correa and Steven N’Zonzi before showing quick reflexes to produce a one-handed save on the stroke of half-time and deny Luis Muriel’s header.
United, who were playing their first Champions League knockout game in four years, offered little offensively, with Romelu Lukaku spurning their best chance when he volleyed well over early on before substitute Marcus Rashford dragged a shot wide in the closing stages.
Paul Pogba started on the bench for the visitors, but came on after just 17 minutes following an injury to Ander Herrera.
Sevilla finished the game with 25 attempts on goal but a mixture of De Gea’s saves and poor finishing from the hosts left them frustrated at the final whistle.
Manchester United will be the happier of the two teams heading into the return leg at Old Trafford on Tuesday, 13 March with Jose Mourinho’s side winning 15 of their 18 games on home soil this season.
Once again, it was the absence of Pogba from the Manchester United starting line-up that dominated the build-up to the game.
Pogba missed Saturday’s 2-0 FA Cup win at Huddersfield because he was unwell but had been expected to return to the first XI in Seville.
Instead, the £89m midfielder was named on the bench, with Mourinho saying Pogba’s illness “created some doubts” about whether he could start on Wednesday.
The France midfielder has struggled for form in recent weeks and had little impact on this game after his early introduction because of Herrera’s injury.
However, it was not the sort of a game where his influence would perhaps be obvious.
United set up to defend deep, with Mourinho appearing to prioritise keeping a clean sheet over scoring an away goal. It wasn’t pretty but it was an effective away performance.
