Small and medium-sized enterprises (SMEs) are central to employment creation and economic diversification in Africa, yet their growth is constrained by the conditions under which they operate. This study examined the effects of the business environment and macroeconomic stability on SME growth in Nigeria, Ghana, Kenya and Rwanda from 2010 to 2025. Specifically, the study assessed the effects of institutional quality, ease of doing business, inflation rate, exchange-rate volatility and interest rate on SME employment growth. The study adopted an explanatory longitudinal design and employed a two-way fixed-effects panel model on secondary data, accounting for country-specific differences and common annual shocks. Descriptive statistics, correlation analysis and diagnostic tests were conducted, with hypotheses tested at the 5% significance level. The findings showed that institutional quality and ease of doing business had significant positive effects on SME growth, while inflation, exchange-rate volatility and lending interest rates had significant negative effects, leading to the rejection of all five null hypotheses. The study concluded that SME growth in the four countries is jointly determined by institutional, regulatory and macroeconomic conditions. It therefore recommended coordinated improvements in governance, regulatory simplification, price and exchange-rate stability, and targeted credit support to shield SMEs from the side effects of monetary tightening.