The Boeing 727, put into service in 1963, had the distinction of a rear doorway with stairs that could be lowered so that passengers could embark and disembark at rural airports which did not have their own airstairs. As initially designed, this door could be opened even whilst in flight as it is not the usual "plug" style.
In 1971, the hijacker known as DB Cooper famously used the rear door to make his parachute escape mid-flight. According to wikipedia, the CIA also used this feature to drop passengers and supplies mid-flight.
In the wake of the DB Cooper incident and other hijackings, the FAA mandated in 1972 that cooper vanes to be installed to prevent the opening of the rear door while in flight.
Does this make the pre-cooper 727 the last passenger airliner which had a door (either passenger or cargo) that could be normally opened while in flight without first depressurizing the entire cabin?
Small Print: There was a rear cabin, pressurized bulkhead door on the 727 that you had to transit through to get access to the ventral stairways which was in the aft, unpressurized bulkhead. The actual ventral stair door itself was not a "plug" style. Thus the ventral stairways meets the requirement of being able to open in flight (even if you couldn't get there because the rear cabin bulkhead door might not open).
Animated image from wikipedia and cc.