Benfica, recently crowned league and League Cup champions, came to Turin confident of ending a 52-year hoodoo that had seen them lose a total of seven European finals since winning the second of two consecutive European Cups in 1962.
Benfica had stumbled at the last hurdle five times in the European Cup, once in the UEFA Cup (1983) and once in its successor, the Europa League, in 2013 when they lost 2-1 to Chelsea in Amsterdam.
However despite creating the lion's share of chances in a fairly balanced encounter, the 'Benfica Curse' was maintained as Jorge Jesus's men ultimately failed to convert the numerous chances they created at Juventus Stadium.
The match remained scoreless after two 15-minute periods of extra time and when it came to penalties Sevilla -- who claimed the second of their two titles from the Europa League's predecessor, the UEFA Cup in 2007 -- stepped up to the plate in impressive fashion.
Benfica striker Lima got the Portuguese giants off the mark but after Sevilla striker Carlos Bacca fired into the roof of the net to pull level, Sevilla 'keeper Beto dived low to save Oscar Cardozo's tame shot.
Stephane Mbia then sent Jan Oblak the wrong way to make it 2-1, and after Beto saved Rodrigo's tame shot the title was Sevilla's after Frenchman Kevin Gameiro, a late substitute, gave the Spaniards an unassailable 4-2 lead following successful spot kicks from either side by Coke and Benfica captain Luisao.
"I hit it hard and I just hoped it would go in," Gameiro, who moved to Sevilla from French champions Paris Saint Germain last year for 10million euros, told Bein Sports.
"It is a magnificent moment for me and for the team. We targeted this trophy all season and it was not easy but we have achieved it.
"It has turned out to be a great season after a tough start but the team really bonded together and this is the result," added the 27-year-old.
Sevilla can now boast winning three titles from Europe's second-tier club competition having won the Europa League's predecessor, the UEFA Cup, twice in succession, in 2006 and 2007.
In 2007 the Spaniards beat fellow La Liga side Espanyol on penalties.
The Andalusians, coached by Unai Emery, become the first champions of the Europa League to win on penalties.
Their triumph this year is all the more impressive as Emery's revamped side, who only finished ninth in last season's Spanish championship, were given entry because two other clubs failed to meet the financial benchmark set by UEFA.