In 2021, the World Health Organization (WHO) ranked Nigeria among the most polluted nations in the world, an indication of a deteriorating air quality, especially in the major urban areas of the country, which might pose adverse human health impacts. In this study, the Integrated Source Apportionment Method (ISAM) tool in the Community Multiscale Air Quality (CMAQ) model (CMAQ-ISAM) was employed to quantify the contributions of eight emissions sectors to fine particulate matter (PM2.5) and its major components in Lagos during a prolonged severe atmospheric pollution episode (APE) in January 2021. The influence of meteorological conditions on the formation and dispersion of PM2.5 during the APE was also elucidated. Spatially, elevated PM2.5 concentrations were found in the northwestern region of Lagos, an urban area with larger anthropogenic emissions. Residential and industry were the two major sources of PM2.5. Residential contributed the most to total PM2.5 (~40 μg/m3), followed by industry (~20 μg/m3). High concentrations of secondary inorganic aerosols (SIA) at the northwest and upper northern areas of Lagos were majorly attributed to residential and industry sectors. In addition, sulfate accounted for the largest fraction of PM2.5, with residential, industry, and energy being its major sources. Residential, industry, and on-road sectors dominated the contributions to nitrate, while residential and industry were the major contributors to ammonium. Furthermore, the elevated PM2.5 concentrations during the APE were greatly enhanced by unfavorable meteorological conditions. This study provides insights for designing effective emissions control strategies to mitigate future severe PM2.5 pollution episode in Lagos.