The Spanish Primera Liga club took a 2-0 lead into the break with goals from Ariel Ibagaza (18) and a Fernando Torres penalty (41 - pictured).
Aleksandar Simic pulled a goal back for the home side nine minutes after half time, but Diego Simeone restored Atletico's two-advantage on 66 minutes.
The result gives the Madrid club an excellent chance of reaching one of the three finals in the summer European competition.
French side Lille look assured of a place in one of the three finals following a comfortable 3-0 first leg win over Croatian club Slaven Belupo.
Christophe Landrin and Philippe Brunel gave the home side a 2-0 lead inside the first half hour before Milenko Acimovic made it three just after the break to secure victory.
The same could not said for fellow French Ligue 1 club Nantes, who went down to a 1-0 first leg defeat against Slovan Liberec in Czech Republic.
Michal Pospisil scored Liberec's winner on 26 minutes before Nantes finished the match with ten men, as Frederic Da Rocha was sent off mid-way through the second half for Les Canaries.
Schalke's bid to win a second consecutive InterToto Cup title were boosted with a 3-1 first leg win against upstarts Esbjerg in Denmark.
It was the Danish side that took the lead on eight minutes through Jerry Lucena before Schalke new boy Ailton brought the Germans level five minutes before the break.
Mike Hanke then put Die Bundesliga club in front mid-way through the second half before Hamit Altintop gave the visitors a two-goal cushion for the second leg on August 3.
Belgian side Genk were held to a 0-0 first leg home draw by Portuguese side Uniao Leiria.
In the late match in Spain, Villarreal got a second half penalty from Sonny Anderson to earn 1-0 victory over German Bundesliga side Hamburg in their first leg contest.
