Ten-man Lazio came from behind to draw 2-2 at home to Vaslui in the only sniff of an upset in the 24-match programme and Argentine striker Matias Suarez scored a hat-trick in Anderlecht's 4-1 win over AEK Athens.
Colombian striker Falcao, top scorer in the competition last season with 17 goals as he led Porto to the title, set Atletico on their way with a third-minute opener, heading in from Brazilian playmaker Diego's corner.
Former Werder Bremen and Juventus midfielder Diego, on loan from VfL Wolfsburg where he walked out on the team in the last match of last season, slotted home in the 69th minute after Arda Turan cut the ball back.
Two goals by Brazilian Wesley put Romanian underdogs Vaslui ahead at Lazio, who also had Luciano Zauri sent off.
However, the Italians, who had taken the lead through Frenchman and new signing Djibril Cisse, snatched a point when Giuseppe Sculli headed a 71st minute equaliser.
PAOK Salonika were involved in an unusual penalty miss in their 0-0 draw at home to Tottenham Hotspur when Lino converted the first attempt, was ordered to retake the kick because of encroachment and swept his second effort wide.
Vladimir Ivic hit the crossbar late in the game as the Greeks settled for a point.
Athletic Bilbao, starting their first season under eccentric former Argentina and Chile coach Marcelo Bielsa, won 2-1 at Slovan Bratislava with goals from Markel Susaeta and Iker Muniain.
Sporting scored twice in the first 20 minutes to win 2-0 at FC Zurich while Nene, Mathieu Bodmer and Jeremy Menez were on target as Paris Saint-Germain, inspired by Argentine playmaker Javier Pastore, beat Salzburg 3-1.
Stoke City, playing in European competition for the first time since 1972, were denied a win at Dynamo Kiev when Ognjen Vukojevic scored in stoppage-time for the 13-times Ukrainian champions to cancel out Cameron Jerome's earlier effort.
Portuguese striker Hugo Almeida scored twice as Besiktas produced the biggest win of the night, a 5-1 demolition of Maccabi Tel Aviv.
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