This paper explores the impact of the institutional and socioeconomic factors on corruption in the Middle East and North Africa (MENA) and Sub-Saharan Africa (SSA) by employing panel data for the period 2000–2022. Considering corruption as a major impediment to sustainable economic development, this study evaluates the impacts of government effectiveness, democracy, political stability, GDP per capita, young unemployment and literacy on corruption over several time horizons. To assess the robustness of the results, we use panel fixed-effects models and various econometric specifications, in order to isolate short-, medium- and long-term associations. The results indicate that government effectiveness, democracy and GDP per capita are strong drivers of corruption in both regions, with improvements in these parameters resulting in reduced corruption levels. But the impact of political stability, literacy and young unemployment varies between areas and time periods. Political stability reduces corruption in MENA but is positively correlated with corruption in SSA in the short run, although its influence becomes unimportant over longer horizons. In both regions, higher youth unemployment is associated with increased contemporaneous corruption, although its long-run influence remains substantial only in SSA. The results overall emphasize the importance of enhancing government effectiveness, fostering democratic institutions and encouraging sustained economic development as key components of long-term anti-corruption strategies. The observed variations between MENA and SSA further show that strategies to reduce corruption should take into account regional institutional and socioeconomic realities.