Neisseria meningitidis serogroup A accounted for 95% of cases of meningococcal disease in China during the last century. To understand the circulation of these organisms in China over a 50-year period, 275 serogroup A meningococcal isolates collected between 1956 and 2005 were characterised by multilocus sequence typing (MLST) and PorA typing. In total, 44 sequence types (STs), belonging to five hyperinvasive lineages, and ten singletons were identified in this collection. The ST-5 complex and the ST-1 complex represented 52.8% (86/163) and 44.2% (72/163), respectively, of isolates from cases of infection and, overall, 93.1% (256/275) of all isolates. Three prevalent clones (ST-5, P1.5–2,10; ST-3, P1.7–1,10; and ST-5, P1.20,9) were involved in four national epidemics in 1959, 1967, 1977 and 1984. ST-5 was replaced by ST-7 in the late 1980s, such that ST-7 isolates with P1.20,9 represented >86% of isolates from cases of infection after 2000. The data also revealed that the collection contained 19 PorA VR types, of which P1.7–1,10 and P1.20,9 were the predominant types in the ST-1 and ST-5 common lineages, respectively. Three other hyperinvasive lineages (ST-11 complex, ST-32 complex and ST-4821 complex) were isolated only from carriers. It was concluded that serogroup A meningococci of the ST-5 complex and the ST-1 complex were responsible for most cases of meningococcal disease in China during the past 50 years.