A week on from blowing a comfortable two-goal lead in the first leg of their quarter-final, the Red Devils withered rather than rallied at the rocking Estadio Ramon Sanchez-Pizjuan on Thursday.
Youssef En-Nesyri capitalised on a Maguire mistake and, after Loic Bade's header, punished De Gea's slip in a 3-0 win that saw United make a humiliating Europa League exit 5-2 on aggregate.
The Red Devils had knocked out Barcelona and Real Betis to reach this stage, but for the sixth season running their European dreams ended in defeat to Spanish opposition.
Sevilla began that run in 2018 and had the visitors on the backfoot from the outset on Thursday, when Erik ten Hag's call for his players to keep their cool fell on deaf ears.
The home side's pressure forced Maguire into an error from a poor De Gea pass out, with Erik Lamela winning the ball and En-Nesyri striking home in the seventh minute.
Lucas Ocampos had a goal disallowed and abject United were fortunate not to be further behind at the break, only to concede again 76 seconds after the restart.
Bade, who started the season on loan at Nottingham Forest, headed home and the absentee-hit visitors' response was desperate and disjointed as they failed to claw one back.
In fact, things got even worse as En-Nesyri scored from distance into an empty net after De Gea failed to clear a high ball.
Record Europa League winners Sevilla, who will continue their quest for a seventh title, are joined by Bayer Leverkusen who earned a 4-1 win at Union Saint-Gilloise.
Juventus were held to a 1-1 draw at Sporting, but moved into the next stage thanks to the 1-0 win in the first leg.
Sevilla set up a meeting with Juventus, while Leverkusen will face the winner of the tie between AS Roma and Feyenoord.
Leverkusen made it to the semi-finals of the Europa League for the first time ever despite a 1-1 draw at home last week.Â
They had the perfect start as Moussa Diaby found the opener with only two minutes played and Mitchel Bakker doubled their lead in the 38th.
Jeremie Frimpong added a third in the 61st and Casper Terho pulled one back four minutes later but Adam Hlozek sealed the win for the German side.
Juventus and Sporting entertained in their clash on Thursday before the Italians progressed.
Juve took an early lead through midfielder Adrien Rabiot who netted from close range after nine minutes following a corner.
Sporting winger Marcus Edwards equalised from the penalty spot in the 20th minute when he sent keeper Wojciech Szczesny the wrong way with a strike into the middle of the goal after Rabiot was penalised for a tackle on Manuel Ugarte.
A lively clash continued after the break as Sporting pressed with confidence for possession but defenders Ricardo Esgaio and Sebastian Coates squandered three late chances to level the tie.
with DPA/Reuters
10°C