Poultry manure (PM) has demonstrated its potential to enhance crop nutritional quality. Nevertheless, there remains a dearth of knowledge regarding its synergistic effects when combined with wood biochar (B) on the nutrient concentrations in sweet potato leaves (Ipomoea batatas L.) and the mineral content stored in sweet potato storage roots. Hence, a two-year field trial was undertaken during the 2019 and 2020 cropping seasons in southwestern Nigeria, spanning two locations (Owo—site A and Obasooto—site B), to jointly apply poultry manure and wood biochar as soil amendments aimed at enhancing the nutritional quality of sweet potato crop. Each year, the experiment involved different combinations of poultry manure at rates of 0, 5.0, and 10.0 t ha−1 and biochar at rates of 0, 10.0, 20.0, and 30.0 t ha−1, organized in a 3 × 4 factorial layout. The results of the present study demonstrated that the individual application of poultry manure (PM), biochar (B), or their combination had a significant positive impact on the nutrient composition of sweet potato leaves and minerals stored in the sweet potato storage roots, with notable synergistic effects between poultry manure and biochar (PM × B) in enhancing these parameters. This highlights the potential of biochar to enhance the efficiency of poultry manure utilization and improve nutrient utilization from poultry manure. The highest application rate of poultry manure at 10.0 t ha−1 and biochar at 30.0 t ha−1 (PM10 + B30), resulted in the highest leaf nutrient concentrations and mineral composition compared to other treatments at both sites. Averaged over two years, the highest application rate of poultry manure at 10.0 t ha−1 and biochar at 30.0 t ha−1 (PM10 + B30) significantly increased sweet potato leaf nutrient concentrations: nitrogen by 88.2%, phosphorus by 416.7%, potassium by 123.8%, calcium by 927.3%, and magnesium by 333.3%, compared to those in the control (PM0 + B0). The same treatment increased the concentration of sweet potato root storage minerals: phosphorus by 152.5%, potassium by 77.4%, calcium by 205.5%, magnesium by 294.6%, iron by 268.4%, zinc by 228.6%, and sodium by 433.3%, compared to the control. The highest application rate of poultry manure at 10.0 t ha−1 and biochar at 30.0 t ha−1 yielded the highest economic profitability in terms of gross margin (44,034 US$ ha−1), net return (30,038 US$ ha−1) and return rate or value-to-cost ratio (VCR) (263). The results suggested that the application of poultry manure at 10 t ha−1 and biochar at 30 t ha−1 is economically profitable in the study areas and under similar agroecological zones and soil conditions.