[1] Nicknamed El Recreacionista (The Recreationist in Spanish) due to his unorthodox training methods,[2] Osorio held various assistant coaching jobs before beginning his managerial career in 2006 with Millonarios, moving abroad the following year to manage Major League Soccer teams Chicago Fire and New York Red Bulls, leading the latter to their first conference title in 2008.

He led the Bogotá-based club to an 11-6-7 record during the 2007 Finalizacion (closing) season and a fourth-place finish out of 18 teams in the Mustang Cup.

After a promising start, the club qualified for the playoffs on the final day of the season and was seeded as a wild card into the Western Conference bracket.

Due to mounting pressure, Osorio resigned from his post as coach of the New York Red Bulls on 21 August 2009.

[5] On 2 February 2011, Osorio was officially named as the new coach of the Honduras national team and to lead them during the qualifying rounds of the 2014 FIFA World Cup.

On 15 November, the president of Mexican club Puebla Roberto Henaine announced via Twitter that Juan Carlos Osorio would be manager, following Sergio Bueno departure.

On 14 October 2015, after heavy media speculation, Osorio was confirmed as head coach of the Mexico national football team, signing a three-year contract.

[13] On 13 November, Osorio won his first game in charge of Mexico, defeating El Salvador 3–0 at Estadio Azteca in their opening match of the 2018 World Cup fourth-round qualifiers.

[19] In March 2018, it was reported that Osorio had rejected an offer from the Mexican Football Federation to extend his contract with the Mexico national team.

[20] In the 2018 World Cup group stage, he led Mexico to beat the defending champions Germany 1–0, then South Korea 2–1, before losing 3–0 against Sweden; however, they qualified to the round of 16, where they lost 2–0 to Brazil.

Osorio's second spell with the club ended on 1 November 2020 after 20 wins, 18 draws and 12 losses, as he was sacked following a 3–0 defeat to Nacional's rivals Millonarios.

[26] On 31 March 2022, he left his post at the club by mutual consent due to poor results and disagreements on sports project with the board of directors.

[32] On 30 July 2024, Osorio received a four-game ban for violent conduct after he confronted a linesman during a Leagues Cup match.