Background: Previous cross-cultural and mono-cultural studies have reported the prevalence of depressive symptoms to vary across different populations and ethnic groups. Research on prevalence and factors associated with depressive symptoms among adults in the different geopolitical regions of Nigeria is sparse, despite the differences in sociocultural attribute. Aim: The aim was to assess the prevalence and factors associated with depressive symptoms among Yoruba adults in South-Western Nigeria. Methods: Data on 200 Yoruba adults residing in Ile-Ife, Nigeria were collected using a questionnaire composed of socio-demographic data, quality of life (QoL), overall health, perceived stress, and depressive symptoms. Results: The prevalence of depressive symptoms among the respondents was 17.0% (male = 15.9%, female = 18.3%). The depressed respondents reported higher mean scores on all items of the Zung’s self-rating depression scale compared to the non-depressed except in suicidal rumination. Smoking of tobacco was significantly associated depression (P < 0.025). The non-depressed respondents reported significant higher mean scores on overall QoL and overall health compared to the depressed respondents (P < 0.001). However, depressed respondents reported significant higher perceived stress when compared to the non-depressed (P < 0.001). The predictors of depressive symptoms were perceived stress (odds ratio [OR] = 1.409, 95% confidence interval [CI] = 1.167-1.702) and overall health (OR = 0.288, 95% CI = 0.130-0.638). Conclusion: Prevalence of depressive symptoms is high among our sample and factors that significantly predicted it includes high perceived stress and poor self-rated overall health. The findings in this study support the development of interventional strategies targeted specifically at ameliorating stress levels and improving general health at the level of the community.