The nature and type of local indoor resting wall surfaces to certain level influences the residual bio-efficacy of insecticides used in indoor residual spraying programs. Knockdown and mortality effects of an organophosphate Actellic 300 CS and pyrethroid K-Othrine WG 250 insecticides on the field-collected Culex quinquefasciatus were assessed bimonthly from July to November 2014, using World Health Organization (WHO) cones bioassay test. Knockdown and mortality rates were subjected to statistical analysis using χ2 and Student t tests. Result of the bioassay test on C quinquefasciatus showed that plywood surfaces had the best residual knockdown activity of Actellic 300 CS with knockdown rate above the WHO-recommended threshold limit of ≥95% for 30 days after treatment. This was followed by mud surface with knockdown rates ≥95% threshold limit 15 days (97%) after treatment. The lowest knockdown rates of less than 95% were observed on cement surface throughout the assessment period. However, the knockdown rates of mosquitoes on deltamethrin WG 250-treated cement and plywood surfaces were 100% and ≥95%, respectively, at 30 days after treatment. But the knockdown activity was below the recommended threshold limit on mud surface during the 17 weeks trial. Knockdown activities varied significantly (p < .05), and it is a function of exposure periods, different surfaces, and insecticide formulations. The 24-hour mortality rates of Actellic 300 CS and K-Othrine WG 250 at 120 days after treatment were 83.6% and 86.7%, and 80% and 83.3%, on plywood and cement surfaces, respectively. A maximum residual period of 75 and 45 days were recorded for Actellic 300 CS and K-Othrine WG 250, respectively, on mud surface. Both Actellic 300 CS and K-Othrine 250 WG were highly effective against Culex mosquito. The extended residual activity of p-methyl CS compared with deltamethrin WG 250 makes it a suitable alternative insecticide against pyrethroid-resistant mosquitoes in Southwest Nigeria.