Background: Understanding the molecular epidemiology and clinical presentation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) in rural-urban populations in Kenya is important for informing future public health responses and clinical care. Methods: We undertook a retrospective analysis of the clinical presentation and phylogenetic relatedness of specimens from 97 SARS-CoV-2 cases collected between 24^th April and 31^st December 2021 in Laikipia county, Kenya. VOC were related to observed symptoms. Phylogenetic analyses included contemporaneous sequences from across Kenya and the globe, to contextualise local transmission dynamics. Results: These sequences fell into three VOC; Alpha (n=8), Delta (n=52) and Omicron (n=37). We estimated 75 independent SARS-CoV-2 introductions into the county. The Alpha and Delta VOC were commonly detected in persons aged 31 to 45 years, 50.0% and 30.8%, respectively. The Omicron VOC was mostly detected in 16 to 30-year-olds (51.4%). Whereas relative to the other VOCs, Omicron was associated with mild upper-respiratory tract symptoms (cough, OR 3.78; 95% CI 1.1 – 16.74, p= 0.026) and sore throat, OR 22.42; 95% CI 7.11 – 81.40, p<0.001), Delta was associated with moderate to severe lower-respiratory tract symptoms (shortness of breath, OR 26.8; 95% CI 3.89 – 1158.14, p<0.001) and fever (OR 6.11; 95% CI 1.57 – 35.35, p= 0.004). Post-acute phase neurological complications were suspected in four Delta infected cases (neuralgia, neuritis, peripheral neuropathy, numbness of hand and tinnitus). Conclusion: We highlight the distinctive clinical characteristics of SARS-CoV-2 VOCs, as observed in Laikipia, Kenya, to support evidence-based clinical decisions. Multiple introductions of the VOCs were recorded despite the public health measures that were in place questioning their effectiveness during the study period.