While intended as a high altitude fighter, the PB-2 flew relatively few high altitude flights, partly because of the discomfort for the crew. One exception took place in March 1937, when a PB-2A was flown to 39,300 feet (12,000 m) before being forced to return to lower altitudes when the aircraft's controls froze. On 17 October 1936, a PB-2A flown by Lt. John M. Sterling won the Mitchell Trophy air race with a speed of 217.5 miles per hour (350.0 km/h). Since the PB-2A was one of the few aircraft at the time to have retractable landing gear, they were frequently damaged in "wheels-up" landings when the pilots forgot to extend the landing gear.
One PB-2A was modified to a single-seat configuration as the PB-2A Special, to compete in a 1936 Air Corps competition for a new fighter to replace the Boeing P-26 Peashooter. It was larger and heavier than the other competitors and was much more expensive. It crashed during testing, with the Seversky P-35 being ordered into production. One A-11 was converted to the XA-11A testbed with the new 1,000 hp (746 kW) Allison XV-1710-7 engine.
While the PB-2 was sturdy, the two-seat fighter concept was obsolete by the time the aircraft entered service, and by 1939, all had been replaced in front-line service by Seversky P-35 and Curtiss P-36 Hawk aircraft. The survivors remained in use as training aircraft until after the start of World War II, with the last being withdrawn from use on 2 June 1942.