Rueda is one of the most successful Colombian coaches of all time and led Atletico to the Copa Libertadores title in 2016. They also reached the final of the Copa Sudamericana the same year.
"These have been an unforgettable two years because we have won things we have never won before," the departing coach told reporters.
"I believe that I have completed a successful cycle. A breath of fresh air will now blow through the institution. And I am going to get some oxygen too."
His successor Lillo was most recently assistant to Jorge Sampaoli at Sevilla and also has managerial experience in Mexico and Colombia, where he coached Millonarios.
(Reporting by Andrew Downie; Editing by Toby Davis)
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