Serogroup B invasive meningococcal disease (IMD) is increasing in China, but little is known about the causative meningococci. Here, IMD and carriage isolates in Shanghai characterised and the applicability of different vaccines assessed. Seven IMD epidemic periods have been observed in Shanghai since 1950, with 460 isolates collected including 169 from IMD and 291 from carriage. Analyses were divided according to the period of meningococcal polysaccharide vaccine (MPV) introduction: (i) pre-MPV-A, 1965-1980; (ii) post-MPV-A, 1981-2008; and (iii) post-MPV-A + C, 2009-2016. Over this period, IMD incidence decreased from 55.4/100,000 to 0.71 then to 0.02, corresponding to successive changes in meningococcal type from serogroup A ST-5 complex (MenA:cc5) to MenC:cc4821, and finally MenB:cc4821. MenB IMD became predominant (63.2%) in the post-MPV-A + C period, and 50% of cases were caused by cc4821, with the highest incidence in infants (0.45/100,000) and a case-fatality rate of 9.5%. IMD was positively correlated with population carriage rates. Using the Bexsero Antigen Sequence Type (BAST) system, fewer than 25% of MenB isolates in the post-MPV-A + C period contained exact or predicted cross reactive matches to the vaccines Bexsero, Trumenba, or an outer membrane vesicle (OMV)-based vaccine, NonaMen. A unique IMD epidemiology was seen in China, changing periodically from epidemic to hyperepidemic and low-level endemic disease. At the time of writing, MenB IMD dominated IMD in Shanghai, with isolates potentially beyond coverage with licenced OMV- and protein-based MenB vaccines.