Rice production in the karst dryland is still low, due to soil characteristics that lack nutrient availability. Meanwhile, upland rice has received less attention, and it has not been used to its full potential. This study aimed to evaluate the effect of various combinations of inorganic fertilizers, poultry manure, and upland rice varieties on the production and economic value of karst dryland in Gunungkidul, Yogyakarta. This experiment was arranged in a factorial design, with inorganic fertilizers, poultry manure, and upland rice varieties set in a randomized block design with three replications. The first factor was a combination of inorganic and organic fertilizer rates: 72 N kg ha−1 + 26 P2O5 kg ha−1 + 25 K2O ha−1 + 3 t ha−1 organic, 92 N kg ha−1 + 36 P2O5 kg ha−1 + 30 K2O kg ha−1 + 2 t ha−1 organic, 112 N kg ha−1 + 46 P2O5 kg ha−1 + 35 K2O kg ha−1 + 1 t ha−1 organic. The second factor is the upland varieties of Inpago 8, Inpago 10, and Inpago 12 and lowland variety Inpari 42 Agritan GSR, as checked. Based on the study, we concluded that the combination of 92 N kg ha−1 + 36 P2O5 kg ha−1 + 30 K2O kg ha−1 + 2 t ha−1 poultry manure fertilizers with Inpago 8 resulted in an IDR profit of 23,586,000 ha−1, and it is the most recommendable fertilizer and variety combination to be developed in the karst dryland, in consideration of land fertility and sustainability.