The 1980–81 FA Trophy was the twelfth season of the FA Trophy.
The teams that given byes to this round are Dagenham, Altrincham, Weymouth, Worcester City, Boston United, Gravesend & Northfleet, Maidstone United, Kettering Town, Bangor City, Nuneaton Borough, Yeovil Town, Barrow, Stafford Rangers, Matlock Town, Bedford Town, Runcorn, Enfield, Wycombe Wanderers, Leatherhead, Tooting & Mitcham United, Spennymoor United, Marine, Blyth Spartans, Cheltenham Town, Mossley, Barking, Chorley, Walthamstow Avenue, Dulwich Hamlet, Sutton United, Woking and Ashington.