Prioritization of climate change adaptation options is complex. This study presents a multi-dimensional decision framework to evaluate how best to allocate resources among competing alternatives. The main objectives were to identify the prioritized climate-smart agricultural practices adopted among smallholder farmers in different value chains across sub-Saharan Africa and to assess the economic feasibility of the practices using Cost-Benefit Analysis. The main aim was to develop a portfolio of viable and cost-effective options. This study focused on five sub-Saharan African countries and selected value chains (Ethiopia: Faba beans, Kenya: Sweet potatoes, Malawi: soybean, peanut, cassava, Nigeria: potato and rice, and Zambia: soybean, peanut). A sample of 153 smallholder farmers was interviewed across the five countries including stakeholders within Green Innovation Centres. The Climate Smart Agriculture Prioritization Framework was applied for the assessment of economically viable adaptation options. The prioritization was based on standard ranks on the ability of the practice to improve productivity, increase resilience, and mitigation benefits. Spearman’s rank-order correlation was used to assess the independence of the ranks. A Cost-Benefit Analysis was conducted as the final step. Evidence suggests that smallholder farmers in the study areas prioritized the adoption of improved seed, good agricultural practices, and conservation agriculture practices. In the sweet potato value chain in Kenya, the use of good agricultural practices was viable with a net present value of US$ 28,044, an internal rate of return of 328%, and a one-year payback period. This is in comparison to the improved seed varieties (US$ 8,738, 111%, and two years respectively). In Nigeria, the most viable option was the improved seed in the potato value chain and good practices in the rice value chain. In Malawi, Ethiopia, and Zambia, the most viable practices were improved seed, and conservation agriculture in the soybean, faba beans, and peanut value chains respectively. The net present value was highly sensitive to changes in the discount rate, moderately to price, yield, and practice lifecycle, and least to changes in annual labour costs. The results from this study elaborate on the most feasible adaptation practices that enable smallholder farmers increase productivity and be economically efficient.