Human malaria is a major cause of morbidity and mortality in sub-Saharan Africa. The present study explored the dynamics of malaria infection relative to Anopheles mosquito abundance, relative humidity and temperature in Nsukka, Nigeria. Hospital records from three hospitals in Nsukka town: Bishop Shanahan Hospital, University of Nigeria Medical Centre and Sadiq Hospital were examined for malaria prevalence and intensity from January to July 2015. Indoor biting Anopheles mosquitoes were collected by standard procedures within the study duration. Meteorological data on relative humidity and temperature was obtained from Centre for Basic Space Science, Nsukka, Enugu State. Overall recorded malaria prevalence at the hospitals from January to July was 72.8%. Malaria prevalence was highest in the month of July (90.3%) and least in February (55.4%). Majority of these infections were mild. Overall, more females compared to males were infected in the hospitals sampled (p < 0.01). Peak abundance of Anopheles mosquitoes was in July and lowest in January. Relative humidity increased from January to July while temperature declined in same direction. Malaria prevalence correlated positively with Anopheles mosquito abundance (r = 0.863, p = 0.012). Mosquito abundance and malaria prevalence strongly correlated negatively with temperature (r = -0.799, p = 0.031 and -0.869, p = 0.011, respectively). The positive correlation between relative humidity and malaria prevalence and mosquito abundance was not significant (p < 0.05). Malaria prevalence in Nigeria is influenced by Anopheles mosquito abundance. This association is affected by variation in temperature and relative humidity of the environment.