Flames broke out Sunday night around 8:30 at 1354 N. Church Street.
A woman was pulled unresponsive from the burning home and died while a man was flown to Lehigh Valley Hospital for treatment.
At least one pet also died in the fire.
Meanwhile, Route 309 was closed in both directions near the fire scene.
Drivers were urged to use Airport Beltway or Route 940 to Hillside Drive as detours.