Reaching the May 24 showpiece in Lisbon is a remarkable achievement for Diego Simeone's unfancied side, who will be chasing Atletico's debut triumph in Europe's elite club competition.
It will be their second appearance in the final after they were beaten in the only European Cup final to be replayed by Bayern Munich in 1974.
Real, the world's richest club by income with revenue almost five times that of Atletico, are bidding for a record-extending 10th continental crown in their 13th final and first since they last won the trophy in 2002.
Atletico also remained on course for an unlikely double as they are top of La Liga wdith three games left.
Real, who beat Barcelona to win this month's King's Cup, are six points behind in third with a game in hand and could still become only the second Spanish side after the 2008-09 Barca team to win a treble of domestic league and cup and Champions League.
Atletico's success is in large part down to the inspirational leadership of Simeone, who played for the club when they won a league and cup double in 1996.
The Argentine's Real counterpart Carlo Ancelotti, in his first season in charge after taking over from Jose Mourinho, plays a less prominent role but has won plaudits for fostering a harmonious dressing-room atmosphere.
Real's expensively assembled squad, including the likes of Cristiano Ronaldo and Gareth Bale, have thrived on the stability, a marked contrast to Mourinho's divisive three years at the helm.
Their 5-0 aggregate destruction of holders Bayern in the semi-finals prompted the Madrid-based sports media to all-but proclaim them champions of Europe.
If Atletico defy the odds and deny their crosstown rivals a 10th European title - what has become known as the 'decima' in Spain - it would be a spectacular upset and by far their greatest achievement.
It would also be a sign that spending hundreds of millions of euros on players is not the only path to success.
Atletico, who won the Europa League in 2010 and 2012, have just about had the better of recent meetings with Real, beating them 2-1 after extra time at their own Santiago Bernabeu stadium to win last season's King's Cup.
They followed that up with a 1-0 win at Real in La Liga in September before last month's 2-2 draw at Atletico's Vicente Calderon arena.
However, Real knocked them out 5-0 on aggregate in the last four of the King's Cup.
The game in Lisbon will not be the teams' first European battle - but it will be the first for 55 years since they met in the semi-finals of the 1958-59 European Cup.
Real, who won the first five European Cups, beat Atletico 2-1 in a replay in Zaragoza with goals from Alfredo di Stefano and Ferenc Puskas after the teams finished 2-2 on aggregate in the days before the introduction of the away goals rule.
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