The airport was inaugurated on 11 June 1938. The airport's runway was constructed in the 1960s, and was resurfaced in 1985. Spanish airline Iberia provided direct flights to Asunción from Madrid from around 1968 until the mid-1990s. Lufthansa flew once a week from Frankfurt to Asunción from 1971 to 1980, with DC-10 service starting in 1974. For both airlines, the flights included multiple stops in destinations throughout South America. Also, between the early 1990s and 1996, Lineas Aereas Paraguayas flew nonstop to Frankfurt with its DC-10. In November 2004, the director of Direccion Nacional de Aeronautica Civil (DINAC), Eustaquio Ocáriz, told ABC Color that the airport's runway, which had repair work started in 2001, but halted due to lack of funds, would be completed by the early months of 2005. On 31 July 2007, at 05:10am, a group of five men stole US$1,000,000 from a money exchange on the bottom floor of the airport. One of the robbers, Juan Pablo Ortigoza, was detained, along with others. Another robber was captured in Encarnación. It was later discovered that the robbery was planned in Asunción's Tacumbú prison. One of the arrested stated they received US$60,000 for the robbery. The money was going to be sent on a flight to Uruguay. In May 2008, a report concluded that Paraguay's aeronautic systems were in a critical state and needed to be replaced. In November 2009, new instrument landing systems began operating. The equipment was acquired at a cost of €967,400. The previous system that was replaced was installed in 1980. The implementation of the system made Paraguay up to date with the requirements of international security as a member of the OACI. In January 2013, various improvements were made to the terminal. By 2015, some airlines had ceased operations at the airport, including American Airlines. On 17 December 2015, Air Europa began service between Pettirossi and Madrid, Spain, creating the first direct connection between Paraguay and Europe in 21 years. In 2017, airport infrastructure specialist Carlos Achucarro estimated that the airport would require expansion before 2024. In January 2018, DINAC reported that the airport has seen a 15 percent rise in travellers from 2013 to 2017. The airport also saw an increase in flights, from 20 daily flights to about 60 flights by 2018. Pettirossi Airport ceased operating commercial flights for 7 months due to the COVID-19 pandemic. In October 2020, DINAC announced a ceremony for the resumption of flights. In November 2020, five packages containing drugs were found by agents of the National Secretary of Antidrugs; one of the packages was destined for Sri Lanka and two each for Australia and Hong Kong. In February 2021, plans for a second terminal were unveiled, to be started in 2022. In October 2021, a new route, operated by Paranair, was announced between Pettirossi and Santa Cruz de la Sierra, Bolivia.