Panagra's network stretched from Panama and the U.S.-controlled Panama Canal Zone to Santiago, Chile and Buenos Aires.[1] It was founded in 1929 to compete with SCADTA, a German-owned company, and held a quasi-monopoly over air travel in parts of Colombia and South America during the 1940s and 1950s.

In 1939, a passenger traveling from the U.S. to Buenos Aires would board a Pan Am Sikorsky S-42 flying boat at Miami and fly to Colon, Panama in the Canal Zone, stay overnight and then board a Panagra Douglas DC-2 or DC-3 and fly to Buenos Aires with overnight stops in Guayaquil, Arica and Santiago.[2] This routing was a full day faster than the Pan Am service operated via the coast of Brazil. The one-way fare from Miami to Buenos Aires was US $550 (equivalent to $10,245 in 2016).[3]

After World War II, airliners could operate at night over South America, and in 1947 Panagra Douglas DC-6s made scheduled flights from Miami to Buenos Aires in 20 hours and 25 minutes. Pan Am crewed the DC-6 south across the Caribbean to Albrook Field, near Balboa, Panama where Panagra flight crews took over. In 1949, Panagra flights serving Panama shifted to Tocumen Airport. In 1955, Panagra Douglas DC-6Bs and DC-7Bs began serving Washington DC and New York City with these flights being operated by National Airlines crews north of Miami. In 1957, the Panagra DC-7B service via Lima was several hours faster from New York Idlewild Airport (later renamed JFK Airport) to Buenos Aires than the Pan Am DC-7B service operated via Rio de Janeiro.

Panagra entered the jet age in 1960 when it introduced new Douglas DC-8-31 jetliners.[4]

According to the Panagra system timetable dated July 15, 1966, the airline was operating DC-8 "El Inter Americano" jet service between various destinations in Latin America and Los Angeles (LAX), Miami (MIA), New York City (JFK) and San Francisco (SFO).[5] Panagra was still cooperating with National Airlines and Pan American World Airways with regard to their service between the U.S. and Latin America at this time. This timetable listed the following destinations served by Panagra in Central and South America: Antofagasta, Chile; Buenos Aires, Argentina; Cali, Colombia; Guayaquil, Ecuador; La Paz, Bolivia; Lima, Peru; Panama City, Panama; Quito, Ecuador; and Santiago, Chile.

Panagra merged with Braniff International Airways in 1967. Braniff operated the former Panagra routes to South America until 1982 when Eastern Air Lines purchased Braniff's South American operations. Beginning in 1990, these routes were then operated by American Airlines which had acquired them from Eastern.

W. R. Grace and Company had a 50% share of Pan American-Grace Airways, with Pan Am owning the other 50%.