The Cottagers' European campaign started on 30 July 2009 with a 3-0 win at FK Vetra but, on May 12 2010, they were undone by Diego Forlan.
The Uruguay international scored both the Spanish side's goals but it was Sergio Aguero who was the star of the show.
Roy Hodgson's men had beaten the likes of Shakhtar Donetsk, Juventus, Wolfsburg and Hamburg to reach the final but were finally edged out by the mid-table La Liga side that started the season in the Champions League.
After finishing third in their group and being demoted to the Europa League in the new year, Atletico saw off the likes of Valencia and Liverpool to reach the final.
The La Liga side dominated the first half and almost took the lead in the 12th minute. Danny Murphy gave the ball away on the halfway line, allowing Aguero to burst forward.
The Argentinian eventually laid the ball off to Forlan whose shot beat Mark Schwarzer only to hit the outside of the post before bouncing out for a goal kick.
Four minutes later Schwarzer had to scurry across his goal-line to claim Jose Antonio Reyes' curling free-kick and, when Fulham responded, Bobby Zamora headed the ball on to Zoltan Gera who lashed an acrobatic volley over the bar.
Midway through the first half, Atletico keeper David De Gea had his palms stung by Simon Davies' rasping effort before the Spanish side deservedly took a 32nd-minute lead when Aguero's shot, which was going wide, was turned home by Forlan, who looked suspiciously offside.
Fulham have a habit of coming from behind in Europe though and, as against Juventus and Hamburg earlier in the competition, they did so again.
Just five minutes later Zamora made the initial break and, after the move appeared to have broken down, the ball broke to Davies who lashed his shot past De Gea.
Fulham were lucky to be level at half-time but they edged the second half and,
eight minutes after the interval, Gera beat the offside trap only for the Hungarian's touch to be too strong allowing De Gea to race off his line to claim the ball.
On the hour, De Gea made a stunning save, getting down well to deny Davies a second goal but the second period was a very even affair.
The extra 30 minutes were equally tight with clear-cut chances few and far between although the outstanding Aguero was a constant thorn in the Cottagers defence.
He was only just unable to turn Forlan's cross into the net at the end of the first period of extra-time but, in the 116th minute of an absorbing game, he found the energy to cross for former Manchester United striker Forlan to flick a clever shot past Schwarzer and end Fulham's dreams.