In July 1950, the XC-99 flew its first cargo mission, "Operation Elephant." It transported 101,266 pounds (45,933 kg) of cargo, including engines and propellers for the B-36, from San Diego to Kelly Air Force Base in San Antonio, Texas, a record it would later break when it lifted 104,000 lb (47,200 kg) from an airfield at 5,000 ft (1,500 m) elevation. In August 1953, the XC-99 would make its longest flight, 12,000 mi (19,000 km), to Rhein-Main Air Base, Germany, by way of Kindley Air Force Base, Bermuda and Lajes Field in the Azores. It carried more than 60,000 lb (27,000 kg) each way. It attracted much attention everywhere it flew.
The US Air Force determined that it had no need for such a large, long-range transport at that time, and no more were ordered. The sole XC-99 served until 1957, including much use during the Korean War. It made twice weekly trips from Kelly AFB to the aircraft depot at McClellan Air Force Base, California, transporting supplies and parts for the B-36 bomber while returning by way of other bases or depots making pick-ups and deliveries along the way. During its operational life, the XC-99 logged over 7,400 hours total time, and transported more than 60 million pounds (27,000 metric tons) of cargo. The aircraft made its last flight on 19 March 1957, landing at Kelly Air Force Base, where it would remain for the next 47 years. The then-United States Air Force Museum at Wright-Patterson Air Force Base near Dayton, Ohio, requested that the aircraft be flown there for display, but the Air Force refused due to the $7,400 cost of the flight.