There are minimal data on the burden of Streptococcus pyogenes (group A Streptococcus; GAS) in sub-Saharan Africa and none on serotypes causing disease. We analyzed systematically collected clinical and microbiological surveillance data from 64,741 hospital admissions in Kilifi, Kenya (1998-2011), to describe incidence, clinical presentations and emm-types of invasive GAS (iGAS). There were 370 cases; commonly skin and soft tissue infections (258/369,70%), severe pneumonia (86/369,23%), and primary bacteremia (53/369,14%); overall case fatality risk was 45/369 (12%). Incidence of iGAS was, in neonates 0.6/1000 live-births; <1 year 101/100,000, and <5 years 35/100,000. Using genome sequencing, 88 different emm-types were observed, highlighting extensive circulating GAS heterogeneity. GAS is an important cause of serious bacterial disease in this setting, especially in neonates, with considerable genotypic diversity. There may be limited benefit from the most advanced GAS type-specific vaccines and efforts must be directed to protect against disease in high burden regions.