Germany led the recent effort to lease An-124s for NATO strategic airlift requirements. Two aircraft are leased from SALIS GmbH as a stopgap until the Airbus A400M is available. Under NATO SALIS programme NAMSA is chartering six An-124-100 transport aircraft. According to the contract An-124-100s of Antonov Airlines and Volga-Dnepr are used within the limits of NATO SALIS programme to transport cargo by requests of 18 countries: Belgium, Hungary, Greece, Denmark, Canada, Luxembourg, Netherlands, Norway, United Kingdom, Poland, Portugal, Slovakia, Slovenia, Finland, France, Germany, Czech Republic and Sweden. Two An-124-100s are constantly based on full-time charter in the Leipzig/Halle airport, but the contract specifies that if necessary, two more aircraft will be provided on six days notice and another two on nine days notice. The aircraft proved extremely useful for NATO especially with ongoing operations in Iraq and Afghanistan.
United Launch Alliance (ULA) contracts the An-124 to transport the Atlas V launch vehicle from its facilities in Decatur, Alabama to Cape Canaveral. ULA also uses the An-124 to transport the Atlas V launch vehicle and Centaur upper stage from their manufacturing facility in Denver, Colorado to Cape Canaveral and Vandenberg Air Force Base. Two flights are required to transfer each launch vehicle (one for the Atlas V main booster stage and another for the Centaur upper stage). It is also contracted by Space Systems Loral to transport satellites from Palo Alto, CA to the Arianespace spaceport in Kourou, French Guiana.
Airbus Transport International, a subsidiary of Airbus, has selected another Russian cargo company, Polet Airlines as "designated carrier" to the company. Polet expects its three An-124-100s will transport astronautic equipment manufactured by EADS, which is Airbus' parent company, and components of the Airbus A380 superjumbo.
As of 2013 the An-124 has visited 768 airports in over 100 countries.
- On May 1987, an An-124 set a world record, covering the distance of 20,151 km (10,881 nmi) without refuelling. The flight took 25 hours and 30 minutes; the takeoff weight was 455,000 kg.
- In July 1985, an An-124 carried 171,219 kg (377,473 lb) of cargo to an altitude of 2,000 m (6,600 ft) and 170,000 kg to an altitude of 10,750 m (35,270 ft).
- An An-124 was used to transport the Obelisk of Axum back to its native homeland of Ethiopia from Rome in April 2005.
- An An-124 was used to transport an EP-3E Aries II electronic intelligence aircraft from Hainan Island, China on 4 July 2001 following the Hainan Island incident.
- In July 2010, an An-124 was used to transport four 35-foot and three 21-foot skimmer boats from France to the US to assist with the clean-up of the Deepwater Horizon oil spill
- An An-124 was used in April 2011 to airlift a large Putzmeister concrete pump from Germany to Japan to help cool reactors damaged in the Fukushima nuclear accident. The An-225 was used to transport an even larger Putzmeister concrete pump to Japan from the United States.