The Spanish side took a two-goal lead with strikes within four minutes of each other in the first half. Machin Vitolo opened the scoring, then Marko Marin, on loan from Chelsea, doubled the lead.
A United side shorn of many first-choice players two days ahead of the FA Community Shield improved after several substitutions, and Antonio Valencia pulled a goal back on 65 minutes when set up by impressive 18-year-old Belgian midfielder Adnan Januzaj.
But despite an impressive display late in the match, United's defeat was sealed when Bryan Rabello added a third in stoppage time.
Prior to the double blow of Sevilla's opening two goals, Chilean teenager Angelo Henriquez fired straight at Beto after being sent clean through, while afterwards, Shinji Kagawa should have found the net after being picked out at the far post by Valencia, only to be thwarted by the visitors' keeper.
Valencia blazed over in first-half stoppage time before Januzaj was off target with a curling effort just after the break.
Januzaj's presence, along with that of Jesse Lingard, who was introduced at
half-time, was a reminder of two young stars that have shone during pre season.
And the pair combined as the Belgian forced another good save out of Beto before nipping onto the rebound and crossing for Valencia to finish off.
Lingard just failed to finish off Fabio's low cross as he slid in at the far
post, while a more experienced United outfit - bolstered by the introductions of Ryan Giggs, Michael Carrick, Phil Jones and Wilfired Zaha - began to take control.
Zaha and Carrick both had opportunities to level near the end but were unable to take them.
Restored to England's senior squad for next week's friendly with Scotland, Zaha almost brought United level three minutes from time, only for Beto to make another smart save.
In the end, Rabello ensured there was no way back for United.