The 280T was similar to the 26T, using the Breguet 19's flying surfaces combined with a passenger-carrying fuselage that completely filled the interplane gap. The 280 fuselage was based on the 26T's fuselage but featured refined aerodynamics.
A single prototype was evaluated in autumn 1928, followed by eight production machines ordered by Air Union. These were flown on routes between Paris and southern France, between Paris and Switzerland, and (occasionally) between Paris and London. They were joined in service by a 10th machine (converted from one of the 281T prototypes), and six 284Ts with more powerful engines (one of these converted from the other 281T). Two of this latter type were also operated by Air Orient on routes to East Asia. Some of Air Union's 280Ts and 284Ts were still in service when the airline was absorbed into Air France.
On 17 January 1931, Breguet 280T F-AIVU of Air Union crashed whilst attempting to land at Lympne Airport in England. The aircraft caught the boundary fence and crashed onto the airfield, damaging the forward fuselage and undercarriage. Of the eight people on board, one of the crew was injured.