This study aimed to examine the relationship between exposure to childhood sexual abuse (CSA) and the occurrence of mental illness in adulthood in Nigeria. An age- and gender-matched case–control study was conducted in the University of Port Harcourt Teaching Hospital, Nigeria, from January to March 2014. Cases were defined as individuals aged 18 to 60 years diagnosed with mental illness while controls were aged 18 to 60 years who did not have mental illness. The study had 304 subjects comprised of 152 case–control pairs. This case–control study showed a statistically significant association between exposure to CSA and occurrence of mental illness in adulthood (pair-matched odds ratio = 3.25, 95% CI = [1.70, 6.21]). The association between CSA and mental illness was still significant (adjusted odds ratio = 3.11, 95% CI = [1.67, 5.82]) after controlling for family functionality. A robust CSA prevention and treatment strategy that considers the victim and the perpetrator in Nigeria is hereby advocated. This could be achieved by the collaborative efforts of the government of Nigeria and non-governmental organizations.