Neglected tropical diseases (NTDs) such as leprosy, lymphatic filariasis (LF), schistosomiasis and onchocerciasis are endemic in several African countries. These diseases can lead to severe pain and permanent disability, which can negatively affect the economic productivity of the affected person(s), and hence resulting into low economic performance at the macrolevel. Nonetheless, empirical evidence of the effects of these NTDs on economic performance at the macrolevel is sparse. This study therefore investigates the effects of the above-mentioned NTDs on economic performance at the macrolevel in Africa. The study employs a panel design with data comprising 24 to 45 African countries depending on the NTD in question, over the period, 2002 to 2019. Gross domestic product (GDP) is used as the proxy for economic performance (Dependent variable) and the prevalence of the above-mentioned NTDs are used as the main independent variables. The random effects (RE), fixed effects (FE) and the instrumental variable fixed effects (IVFE) panel data regressions are used as estimation techniques. We find that, an increase in the prevalence of the selected NTDs is associated with a fall in economic performance in the selected African countries, irrespective of the estimation technique used. Specifically, using the IVFE regression estimates, we find that a percentage increase in the prevalence of leprosy, LF, schistosomiasis and onchocerciasis is associated with a reduction in economic performance by 0.43%, 0.24%, 0.28% and 0.36% respectively, at either 1% or 5% level of significance. The findings highlight the need to increase attention and bolster integrated efforts or measures towards tackling these diseases in order to curb their deleterious effects on economic performance. Such measures can include effective mass drug administration (MDA), enhancing access to basic drinking water and sanitation among others.