This review evaluated the association of place of residence (urban/rural) and under-five mortality in middle- and low-income countries. Both English and Spanish language studies conducted during the Millennium Development Goal (MDG) period (1990 to 2015) were reviewed. Twenty-six cross-sectional studies, all in the English language, were selected for further review. Published data were used for this analysis. A funnel plot was produced to ascertain the presence of publication bias. The combined relative risk for under-five mortality was estimated using a random-effects model and a meta-regression was conducted on 15 of the 26 studies. The studies had a combined effect size of 1.47 (95% confidence interval, 1.27–1.67). The results of the meta-regression showed a positive association between the relative risk and the percentage of the rural population for the various regions/countries. The coefficient for the variable rural population percentage was 0.007, indicating that for every one percent increase in the rural population percentage, there was a 0.007 increase in the relative risk for under-five mortality. However, this was not significant (p-value = 0.3). Rural disadvantage persists in middle- and low-income countries. This is important to evaluate policies and programmes designed to remove the gap in under-five mortality rates between urban and rural areas.