Jules Kounde and Ivan Rakitic scored two amazing goals in either half as the Rojiblancos go to Camp Nou next month with a significant advantage.
Barcelona were visibly fatigued and struggled to create too many openings, with skipper Lionel Messi also frustrated by Bono, who denied him on two occasions with excellent saves.
Ronaldo Koeman's side now has a huge deficit to overcome at home in three weeks as Sevilla are dreaming of a first Copa del Rey final since 2018.
On that note, here are the five hits and flops from either team:
Hit: Jules Kounde (Sevilla)
If it wasn't clear already, the 22-year old French defender once again demonstrated his talent with a defensive masterclass.
Excellent in the air, composed in possession and always anticipating and diffusing Barcelona's attacks, Jules Kounde devoured the mighty visitors with a colossal performance at the back.
He was the bulwark that prevented Barcelona from firing; Jules Kounde made his presence felt at the other end too, with an all-important strike following a dazzling run through the heart of the Blaugrana defence.
Flop: Lionel Messi (Barcelona)
It was a rare off-game for the Blaugrana captain, who looked subdued for most of the match and even saw three of his efforts saved by Bono, including one well-executed free-kick.
Lionel Messi's usual wizardry went missing, as Sevilla dealt with his threat pretty well, and some of his efforts were quite wayward too.
Moreover, in a repeat of that infamous instance from the Spanish Supercup final last month which got him sent off, the Argentine skipper was involved in another physical spat and was lucky to escape a red.
Nevertheless, that moment well and truly summed up Messi's night - one of frustration and disappointment. He now needs to dig his side out of a massive hole in the second leg.