Abstract Human coronavirus OC43 (HCoV-OC43) is a major contributor to seasonal outbreaks of acute respiratory illness (ARI). The origins of locally circulating HCoV-OC43 strains and characteristics of their genetic diversity are unknown for most settings despite significance to effective HCoV control strategies. Between December 2015 and June 2016, we undertook ARI surveillance in coastal Kenya in nine outpatients and one inpatient health facility (HF). Ninety-two patient samples tested HCoV-OC43 positive and forty (43.5%) were successfully sequenced in spike (S) gene region (2,864 long, ∼70%). Phylogenetic analysis confirmed co-circulation of two distinct HCoV-OC43 clades that closely clustered with genotype G (n = 34, 85%) and genotype H (n = 6, 15%) reference strains. Local viruses within the same clade displayed low genetic diversity yielding identical sequences in multiple HF. Furthermore, the newly sequenced Kenyan viruses showed close phylogenetic relationship to other contemporaneous sampled strains (2015–16) including those originating from distant places (e.g. USA and China). Using a genetic similarity threshold of 99.1 per cent at nucleotide level, the HCoV-OC43 strains sampled globally between 1967 and 2019 fell into nine sequence clusters. Notably, some of these clusters appeared to have become extinct, or occurred only sporadically in a few geographical areas while others persisted globally for multiple years. In conclusion, we found that HCoV-OC43 strains spread rapidly both locally and across the globe with limited genetic evolution in the spike gene. Full-genome sequences that are spatio-temporally representative are required to advance understanding of the transmission pathways of this important human respiratory pathogen.