This chapter analyzes the paradiplomacy of Mexico City, the country’s Federal District (Distrito Federal) and capital city, from 2000 to 2016, including the administrations of Andrés Manuel López Obrador (2000–2005), Alejandro Encinas Rodríguez (2005–2006), Marcelo Ebrard Casaubon (2006–2012) and the first four years of Miguel Ángel Mancera (2012–2016). It studies the levels of international activity during these administrations, and the bureaucratic structures, topics and mechanisms of cooperation used by each administration. It explains the change from a modest profile (López Obrador and Encinas) to one of high international activism (Ebrard and Mancera) in Mexico City analyzing the personal characteristics of the chiefs of government.