FedEx Express (FX, Memphis International) retired its last, and also the world's last, MD-10-10(F) on June 4, 2021.

N562FE (msn 46496), a 43.6-year-old aircraft operated in a passenger configuration by American Airlines and Hawaiian Airlines before being converted into a freighter for FedEx in 2004, was last deployed in revenue service on June 2, 2021, flying from Memphis International to San Juan Luis Muñoz Marin and return. Flightradar24 ADS-B data shows that two days later, the trijet was ferried to Victorville for storage. The aircraft is owned by FedEx Express.

The cargo integrator has operated a total of sixty-four MD-10-10(F)s since the delivery of the first unit of the type, N560FE (msn 46938), in late 1999, the ch-aviation fleets history module shows. The aircraft were originally built as passenger DC-10-10s but were converted into dedicated freighters and had their avionics upgraded following the merger of McDonnell Douglas and Boeing. FedEx was the world's only ever operator of the variant.

FedEx had four units of the type remaining at the beginning of 2021 and planned to retire them by the end of May. The first of the quartet was phased out in January 2021 and the subsequent two in late May 2021.

The carrier continues to operate thirteen MD-10-30(F)s, which underwent a similar conversion and upgrade from DC-10-30s. This variant also remains in service with Transportes Aéreos Bolivianos (2L, La Paz El Alto) and Orbis (New York JFK), which have one each in their fleets. FedEx's fleet also comprises fifty-four MD-11(F)s, as well as 324 Airbus and Boeing dedicated freighters.