From 1 January to 31 December 2018, thirty-six institutions around Australia participated in the Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2018 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to methicillin, and to characterise the molecular epidemiology of the methicillin-resistant isolates. A total of 2,673 S. aureus bacteraemia episodes were reported, of which 78.9% were community-onset. A total of 17.4% of S. aureus isolates were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 17.1% which was not significantly higher than the 13.6% mortality associated with methicillin-susceptible SAB (p = 0.1). With the exception of the β-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However in addition to the β-lactams approximately 42% of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin, 36% to ciprofloxacin and approximately 13% resistant to co-trimoxazole, tetracycline and gentamicin. When applying the EUCAST breakpoints teicoplanin resistance was detected in two S. aureus isolates. Resistance was not detected for vancomycin and linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to two healthcare-associated MRSA clones: ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). The ST22-IV [2B] (EMRSA-15) clone is the predominant healthcare-associated clone in Australia. Seventy-eight percent of methicillin-resistant SAB episodes in 2018 were due to community-associated clones. Although polyclonal, approximately 76.3% of community-associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA), ST5-IV [2B], ST45-VT [5C2&5], ST1-IV [2B], ST30-IV [2B], ST78-IV [2B] and ST97-IV [2B]. Community-associated MRSA, in particular the ST45-VT [5C2&5] clone, has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. The ST45-VT [5C2&5] clone accounted for 11.7% of CA-MRSA. As CA-MRSA is well established in the Australian community, it is important that antimicrobial resistance patterns in community- and healthcare-associated SAB are monitored, as this information will guide therapeutic practices in treating S. aureus sepsis.