Lagoons are large bodies of water that provide essential economic and ecosystem services such as fishing, erosion protection, transportation, as well as water for domestic, industrial, and agricultural use, among others. Unfortunately, municipal, agricultural, and industrial waste are often dumped in lagoons, polluting the water and predisposing humans and aquatic organisms to environmental and health hazards. This calls for regular monitoring of lagoons worldwide. This study assessed the water quality of Epe lagoon in Lagos State, Nigeria, with regard to heavy metal contamination. Water samples obtained at three settlements (Epe, Ejinrin, and Agbowa) along the lagoon were treated and subjected to heavy metal analysis using standard protocols. The heavy metals analysed were lead (Pb), copper (Cu), nickel (Ni), cadmium (Cd), and chromium (Cr). The chronic daily intake (CDI), chronic dermal contact (CDC), hazard quotients (HQ), heavy metal index (HMI), and probability of cancer risk (PCR) of the heavy metals were also calculated. The results revealed that the water samples from the three locations contained non-permissible levels of Pb, Cu, Ni, Cd, and Cr. The CDI, CDC, and HQ of the heavy metals via ingestion and dermal contact were within the recommended limits, except for Pb. Meanwhile, the HMI and PCR of all the heavy metals exceeded the permissible limits. The results obtained suggest that Epe lagoon’s water is contaminated with heavy metals and thus poses health hazards. Consequently, there is a need for heavy metal remediation and control in the lagoon.