Initially, Escobar easily adapts to his new life, giving money to the community while ruthlessly killing those who try to break away from his empire. The Colombian police and Escobar engage in massive battles, resulting in high tension and unrest in Colombia. Escobar's rivals in the Cali cartel form an unlikely alliance with ousted members of his own cartel, as well as with a CIA-backed anticommunist paramilitary group. Agent Peña secretly works with this group, who kill members of Pablo's organization and claim responsibility as "Los Pepes". After two of Escobar's top cartel members are caught and betray him, Escobar goes on the run. His bodyguard and he hide in a safehouse, where he celebrates his 44th birthday. When Pablo tries to make contact with his family, the DEA and military track him down via radio triangulation and corner him on the rooftops. Pablo is hit twice in the ensuing shootout, and although he might survive his injuries, a Colombian policeman executes him. Escobar's wife Tata goes to the Cali cartel for their help in leaving the country. Peña returns to the United States and is asked to provide intelligence against the Cali cartel.

Season one chronicles the life of Pablo Escobar from the late 1970s, when he first began Manufacturing cocaine, to July 1992. The show relates the main events that happened in Colombia during this period and Escobar’s relationship to them. It is told through the perspective of Steve Murphy, an American DEA agent working in Colombia. The series depicts how Escobar first became involved in the cocaine trade in Colombia. He was an established black marketeer in Medellín, moving trucks worth of illegal goods (alcohol, cigarettes, and household appliances) into Colombia during a time when this was strictly forbidden, when introduced to Mateo "Cockroach" Moreno, a Chilean exile and underground Chemist, who pitched the idea that they go into Business together, with Moreno producing and Escobar distributing a new, profitable drug—cocaine. They expand beyond Moreno's small cocaine processing lab by building additional, larger labs in the rainforest and, using the expertise of Carlos Lehder, transport their product in bulk to Miami, where it gains notoriety amongst the rich and famous. Soon enough, Pablo develops larger labs and more extensive distribution routes into the United States to supply growing demand. With cocaine's growth into a drug of importance in the American market, one that accounts for a large flow of U.S. dollars to Colombia and escalating drug-related violence in the United States, the Americans send a task force from the DEA to Colombia to address the issue. Murphy is partnered with Javier Peña. The purpose of Murphy's task force is to work with the Colombian authorities, led by Colonel Carrillo, to put an end to the flow of cocaine into the United States. The season ends with Escobar's escape from prison.

IGN gave the second season a score of 7.4 out of 10, calling it "Good" and wrote "It may go overboard with its love of Pablo Escobar, but I can't truly fault the show for taking advantage of its best performer and character – or for scrambling to find an emotional core on a show that can feel rather clinical." Joshua Alston of The A.V. Club lauded the performance of Moura's and said, "While the show never soft-pedals the havoc Escobar created, it makes him surprisingly sympathetic, thanks in part to Moura’s shrewd, affecting performance." Critic Neil Genzlinger of The New York Times said, "Mr. Moura is inscrutably brilliant at the center of it all." Entertainment Weekly's Jeff Jensen also reviewed the series positively, saying, "Where season 1 spanned 10 years, season 2 captures Escobar's last days on the loose. Each tightly packed episode moves quickly without sacrificing richness, chronicling the uneasy alliances and gross tactics employed to snare Escobar." Tim Goodman of The Hollywood Reporter said, "What works in the early going of season two is that the fall is almost always more thrilling, if not engaging, than the buildup. Escobar senses the loss of power and Moura does some of his best work as viewers read the worry and interior thinking on his face."

Season one, comprising 10 episodes, originally aired on August 28, 2015, as a Netflix exclusive. The series was renewed for a second season, which premiered on September 2, 2016, with 10 episodes. On September 6, 2016, Netflix renewed the series for its third and fourth seasons. The third season premiered on September 1, 2017.

The series was announced in April 2014, through a partnership deal struck between Netflix and Gaumont International Television. The series is primarily written by Chris Brancato and directed by Brazilian filmmaker José Padilha, who directed the critically and commercially successful Elite Squad (2007), before directing its sequel in 2010, which became the highest-grossing film ever in Brazil. On September 15, 2017, one of the shows location scouts Carlos Muñoz Portal was reported as having been found murdered with multiple gunshot wounds in his car on a dirt road in central Mexico near the town of Temascalapa. A spokesman for the attorney general in Mexico state said there were no witnesses due to the remote location and that the authorities will continue to investigate. The possibility of narco gangs being involved is being considered.

Narcotics: from late Middle English: from Old French narcotique, via medieval Latin from Greek narkōtikos, from narkoun ‘make numb’. In Spanish, the term narco is an abbreviation of the word narcotraficante (drug trafficker). Before this usage, in the United States, the epithet "narc" (or "narco") referred to a specialist officer of a narcotics police force, such as a DEA agent.

The show received criticism for the quality of the Spanish spoken. Dr. Alister Ramírez-Márquez, a member of the North American Academy of the Spanish Language, faulted the accents, pronunciation, intonation, and incorrect use of Paisa colloquialisms. Speaking of the show's reception in Colombia, Sibylla Brodzinsky of The Guardian stated, "audiences have been bemused by the stars’ ropey accents, irritated by its portrayal of the country's recent history, and – in some cases – simply bored by yet another narco-drama." The Brazilian accent of Wagner Moura was particularly criticized for being incongruent with Escobar's Paisa background. Gisela Orozco of the Chicago Tribune said the show would not engross Latinos due to the mishmash of accents and contrasted Narcos with Pablo Escobar: El Patrón del Mal. In his review of the show, Colombian TV critic Omar Rincón wrote in El Tiempo, "Narcos is the Miami and US vision of NarColombia – something like Trump’s idea of us: the good guys are the gringos ... and the narcos are comically dysfunctional or primitives with bad taste ... Narcos may do well outside Colombia, but here it produces anger and laughter."