The Australian Gonococcal Surveillance Programme, established in 1981, has continuously monitored antimicrobial resistance in Neisseria gonorrhoeae for more than 40 years. In 2021, a total of 6,254 isolates from patients in the public and private sectors, in all jurisdictions, were tested for in vitro antimicrobial susceptibility by standardised methods. The current treatment recommendation for gonorrhoea, for the majority of Australia, continues to be dual therapy with ceftriaxone and azithromycin. In 2021, of isolates tested, 0.9% were reported nationally with decreased susceptibility (DS) to ceftriaxone (minimum inhibitory concentration [MIC] value ≥ 0.06 mg/L). There was one isolate from non-remote Western Australia that was resistant to ceftriaxone (MIC value ≥ 0.25 mg/L). Resistance to azithromycin (MIC value ≥ 1.0 mg/L) was reported nationally in 4.7% of N. gonorrhoeae isolates. This is increased from that reported in 2020 (3.9%) but similar to the percentage reported in 2019 (4.6%). Isolates with high-level resistance to azithromycin (MIC value ≥ 256 mg/L) are identified sporadically in Australia; none were reported in 2021. In 2021, penicillin resistance was found in 38% of gonococcal isolates nationally, and ciprofloxacin resistance in 53%; however, there is considerable variation by jurisdiction. In some remote settings, penicillin resistance remains low; in these settings, penicillin continues to be recommended as part of an empiric therapy strategy. In 2021, in remote Northern Territory, one penicillin-resistant isolate was reported, and in remote Western Australia 2/83 of gonococcal isolates (2.4 %) were penicillin resistant. There were two ciprofloxacin-resistant isolates reported from remote Northern Territory; ciprofloxacin resistance rates remain comparatively low in remote Western Australia (3/83; 3.6 %).