Their Spanish opponents, who live in the shadows of more glamorous neighbours Real Madrid, will be attempting to end a 14-year trophy drought with Uruguay's World Cup-bound forward Diego Forlan spearheading their attack.
The unfashionable west London club will be playing their 19th match in the competition, ending a campaign which has included visits to Lithuania, Bulgaria, Ukraine and Russia.
They nearly fell at the group stage but pulled off a 3-2 win at FC Basel in their last match and have not looked back since, eliminating defending champions Shakhtar Donetsk and Juventus in the process.
Atletico, on the other hand, parachuted into the tournament after being eliminated from the Champions League group stage and have played only eight games on their road to the final.
"They have many great players and tomorrow night we have to be aware we are playing with great quality," said Fulham manager Roy Hodgson. "We think they're a good team and we think we're a good team and we're hoping for a good final."
The Europa League is the rebranded version of the former UEFA Cup and has pleasantly surprised many observers with some dramatic games in the knockout stages.
But it is still the poor relative of the Champions League and many feel the presence of teams who have qualified by failing in Europe's top club competition devalues it.
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