Abstract Background The public health impact of Chikungunya virus (CHIKV) is often underestimated. Usually considered a mild condition of short duration, recent outbreaks have reported greater incidence of severe illness, fatality, and longer-term disability. In 2018/19, Eastern Sudan experienced the largest epidemic of CHIKV in Africa to date, affecting an estimated 487,600 people. Known locally as Kankasha, this study examines the clinical characteristics, risk factors, and phylogenetics of the CHIKV epidemic in Kassala City. Methodology/Principal Findings A prospective cohort of 142 cases (102 adults, 40 children) were enrolled at Kassala Teaching Hospital in October 2018. Clinical information, socio-demographic data and sera samples were analysed to confirm diagnosis, characterise illness, and identify the viral strain. CHIKV infection was confirmed by real-time reverse transcription-PCR in 84.5% (120/142) of participants. Nine had concurrent CHIKV/Dengue virus (DENV) infection and 28.8% had a positive Rapid Diagnostic Test for malaria. Five percent had haemorrhagic symptoms including two children with life-threatening haemorrhage. One CHIKV-positive participant died with acute renal injury. Ninety to 120 days post-illness, 63% of those followed-up were still experiencing arthralgia in one or more joints, and 11% remained moderately disabled using Rapid3 assessment. Phylogenetic analysis showed all CHIKV infections belonged to a single clade within the Indian Ocean Lineage (IOL) of the East/Central/South African (ECSA) genotype. History of contact with an infected person was the only socio-demographic factor associated with infection (p=0.01), suggesting that vector transmission in households is important. Conclusions/Significance The epidemic is estimated to have affected ∼ 50% of Kassala City’s population. Substantial vulnerability to CHIKV remains here and elsewhere in Sudan due to widespread Aedes aegypti presence and mosquito-fostering household water storage methods. This study highlights the importance of increasing awareness of the severity and socio-economic impact of CHIKV outbreaks and the need for urgent actions to reduce transmission risk in households. Author summary Chikungunya is an arboviral disease transmitted to humans by infected mosquitoes and characterised by fever and arthralgia. Although it is generally considered a short self-limiting infection, long term sequelae and severe disease are increasingly recognised. In 2018/19, Eastern Sudan experienced the largest epidemic of Chikungunya in Africa to date, affecting approximately 500,000 people. We undertook a prospective hospital-based cohort study of patients presenting with undifferentiated febrile illness in Kassala city, Sudan, supported by next-generation sequencing. We confirmed that CHIKV was the dominant pathogen, with positive CHIKV RT-PCR in 85% of patients presenting during the 7-day study period. Dengue virus was also circulating with nine CHIKV PCR-positive patients co-infected, and we identified high rates of Plasmodium falciparum malaria infection and CHIKV/malaria co-infection. Genetic sequencing confirmed Indian Ocean Lineage of the East/Central/South African CHIKV genotype. A substantial proportion of participants were admitted to hospital including children with haemorrhage, reflecting the severe phenotype linked to this genotype. Increased understanding of the health and economic burden of Chikungunya is needed, and recognition that severe and occasionally fatal infection exists. With widespread presence of Ae. aegypti and household water storage practices that encourage mosquito breeding, timely actions will be essential to prevent further large outbreaks.