Jose Mourinho turned to Pogba to influence the game at a crucial stage but the France worldwide was arguably United's worst performer and he gave the ball away a number of times in good areas.
In a game that was fraught with missed chances, a second-half brace by substitute Wissam Ben Yedder was enough to send the Spanish side into the last eight of the competition.
At a restless Old Trafford, United never got out of first gear and Sevilla, having dominated the opening leg at home without finding a way to beat David de Gea in a goalless draw, deservedly progressed.
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Porto and Real Madrid both knocked out United at Old Trafford under Mourinho's stewardship and the Portuguese was quick to highlight the club's previous failings after their shock exit. Mourinho's decision to start the Belgium midfielder was perhaps understandable on the basis that the United manager needed somebody to nullify the threat of Sevilla's own towering midfielder, Steven N'Zonzi. "We did our best, we tried, we lost, that's football", he said.
Ben Yedder put Sevilla in front two minutes later when he blasted into the bottom corner before heading in a second shortly after. "We had good periods, we didn't have great control over the game, but I can't say there was anything wrong with my players and their intention to play".
"After 10 to 15 minutes, Sevilla has a good team and can hide the ball in midfield".
Paul Pogba is another who has missed a number of fixtures with a small problem and Mourinho has admitted he still remains a doubt for the Champions League tie. "We are not the only team that invests money in players".
Ben Yedder received Pablo Sarabia's pass and thumped a finish beyond De Gea for his first, and the goalkeeper - instrumental to United's clean sheet in Seville - could not keep out the striker's back-post header four minutes later.