The Swiss Football Association (ASF/SFV) was expanded during the 1980–81 season from 28 to 32 member clubs.
The format in both divisions was that the teams played a double round-robin to decide their table positions.
The Swiss champions would qualify for the 1982–83 European Cup, the runners-up and third placed team would qualify for the 1982–83 UEFA Cup.
The last two placed teams in the NLA were relegated to the NLB for the following season.
[1] The top-tier, Nationalliga A (NLA), was contested by the top thirteen clubs from the previous season and three sides promoted from the second level 1980–81 Nationalliga B, these being Vevey-Sports, FC Aarau and FC Bulle.