Pablo Escobar was one of the most powerful men in the world in the 1980s. Through terror and a network of corruption, he gained almost total control over the police, the army and much of the Colombian government while operating an international cocaine trafficking network. After a series of savage attacks which involved the downing of an aircraft, bounties for killing police and the bombing of government offices in broad daylight, the Colombian government was forced to act. Their solution was the negotiated surrender of Escobar in exchange for a series of concessions such as allowing the kingpin to choose where he would be imprisoned, a site called "La Catedral" in his native Envigado.

Narrated by Univision nightly news anchor Jorge Ramos, Pablo Escobar: Escape from La Catedral is based on a mysterious set of audio tapes containing secretly recorded telephone conversations between Escobar, his cronies, and others during the months between the capo's surrender, eventual escape and death.