Emerging organic contaminants (e.g., active pharmaceutical ingredients and personal care products ingredients) are ubiquitous in the environment and potentially harmful to ecosystems, have gained increasing public attention worldwide. Nevertheless, there is a scarcity of data on these contaminants in Africa. In this study, various types of water samples (wastewater, surface water and tap water) collected from Lagos, Nigeria were analyzed for these chemicals by both target and non-target analysis on an UHPLC-Orbitrap-MS/MS. In total, 109 compounds were identified by non-target screening using the online database mzCloud. Level 1 identification confidence was achieved for 13 compounds for which reference standards were available and level 2 was achieved for the rest. In the quantitative analysis, 18 of 38 target compounds were detected, including the parent compounds and their metabolites. Acetaminophen, sulfamethoxazole, acesulfame, and caffeine were detected in all samples with their highest concentrations at 8000, 5300, 16, and 7700 μg/L in wastewater, 140000, 3300, 7.7, and 12000 μg/L in surface water, and 66, 62, 0.17 and 1000 μg/L in tap water, respectively. The occurrence of psychoactive substances, anticancer treatments, antiretrovirals, antihypertensives, antidiabetics and their metabolites were reported in Nigeria for the first time. These results indicate poor wastewater treatment and management in Nigeria, and provide a preliminary profile of organic contaminants occurring in Nigerian waters. The findings from this study urge more future research on chemical pollution in the aquatic environments in Nigeria.