[5] The airline was established in March 1970 by Luxair, the Salen Shipping Group, Loftleiðir, and various private interests in Luxembourg.

1983 saw the introduction of the CHAMP (Cargo Handling and Management Planning) computer system and the start of some charter passenger flights for the Hajj pilgrimage.

1988 saw the birth of Lion Air, a passenger charter airline established by both Cargolux and Luxair.

In 1997, Luxair was able to increase its share to 34%, while in September that year Lufthansa sold its 24.5% stake to SAir Logistics; and Swissair Cargo made a cooperation agreement with the Luxembourg company.

In 2000 a route was opened to Seoul, South Korea, and in 2001 Wilkens decided to step down as president and CEO of the air company.

[7] In October 2010, Ulrich Ogiermann, the chief executive officer of Cargolux was indicted on suspicion of price-fixing;[8] After pleading guilty, he was sentenced to 13 months in federal prison.

[10] On 8 September 2011, Qatar Airways purchased a 35% share in the company making it the second largest shareholder after Luxair (43.4%).

[24][25][26] Cargo 2000 — an industry group within the International Air Transport Association (IATA) consisting of some 80 major airlines, freight forwarders, ground handling agents, trucking companies and IT providers — announced on 15 March 2012 at its annual general meeting, that Cargolux Airlines International S.A. had gained Cargo 2000 platinum membership status.

[29][30] Cargolux inaugurated a new aerial firefighting business unit in 2024, which will operate a fleet of 12 aircraft, three of which have already been delivered.

[31][32] Also in 2024, Cargolux and Norwegian Air Shuttle signed a contract for more than 140,000 tonnes of e-SAF (e-Sustainable Aviation Fuel) to be supplied by Norsk e-Fuel from 2026.