Some of the historical inaccuracies in the series:
- Roberto Escobar is completely absent from the story. 
- Steve Murphy only arrived in Colombia in 1991. 
- The characters of Cockroach and Lion are completely made-up.
- Horacio Carrillo was not a real person. He was based off on Hugo Martinez, who takes the role of Carrillo in the series following the former's death.
- La Quica's real name is Dadeny Muñoz Mosquera, and not Juan Diego Diaz. He was arrested on September 25, 1991 in New York City for travelling with a fake passport.
- Navegante's real name is Cesar Yusti, and not Jorge Velazquez.
- Ricardo Prisco died in 1991, and was not alive when Pablo escaped the prison. It was Ricardo's brother Conrado Prisco who was the personal physician of Pablo Escobar. Escobar had Conrado killed.
- Pablo did not spend his last days with his father.
- Juan Pablo Escobar was 16 years old at the time of his father's death. His mother didn't meet Gilberto Rodriguez Orejuela after Pablo's death, and instead fled to Mozambique, before relocating to Argentina.
- Javier Peña did not oversee the investigation of the Cali Cartel.
- Daniel Van Ness' real name is David Mitchell.
- The Autodefensas Unidas de Colombia was only established in 1997.
- Miguel Rodriguez Orejuela's son was named William, and William only entered the trafficking business a few years after his father's arrest.
- José Santacruz Londoño wasn't killed by Carlos Castaño Gil, but by the Colombian police.
- Navegante wasn't killed by Jorge Salcedo, according to both Salcedo himself and Chris Feistl, but it is confirmed that Navegante died on the same day Pallomari was found by the DEA. 
- It is unlikely that Gilberto Rodriguez Orejuela wanted his son to stay away from the cartel business, as in real-life, his son Jorge Alberto Rodriguez Herrera headed a secret cell affiliated to the cartel named The 400 in New York City. The 400, as the name suggests, was a group of 400 highly skilled hitmen of different nationalities, supervising cocaine production in New York City. 
- It wasn't Peña, but another DEA agent named Joe Toft who revealed the corruption in Colombia, and called the country a 'narco-democracy'.