The long-term sustainability of e-commerce usage for improving quality of life is dependent on several factors. Presently, trust and payment methods have emerged as critical factors influencing e-commerce adoption. Consequently, this study investigates the UTAUT determinants of consumer e-commerce adoption in Ghana by focusing on the mediating and moderating roles of trust and payment method. The study employs the Partial Least Square Structural Equation Model (PLS-SEM) to estimate the survey response of 535 purposively selected respondents from six regions in Ghana. The results corroborate a direct relationship between the UTAUT variables and e-commerce adoption. However, the payment method suggests no moderating effect on trust and e-commerce adoption connection. Nevertheless, trust significantly mediates the UTAUT variables and e-commerce adoption. Finally, the mediation was highest between social influence and trust but lowest between effort expectancy and trust. This challenges practitioners and managers of e-commerce platforms to consider the mediating role of trust to improve adoption and the sustainable usage of e-commerce.