Calcareous soil had sufficient phosphorus and potassium (PK) in different forms due to the high contents of PK-bearing minerals; however, the available PK state was reduced due to its PK-fixation capacity. Compost, coupled with high PK solubilization capacity microbes, is a sustainable solution for bioorganic fertilization of plants grown in calcareous soil. A 2-year field experiment was conducted to investigate the effect of compost (20 t ha−1) with Aspergillus niger through soil drenching (C-AN) along with partial substitution of PK fertilization on quinoa performance in normal and calcareous soils. Treatments included PK100% (72 kg P2O5 ha−1 + 60 kg K2O ha−1 as conventional rate), PK100%+C-AN, PK75%+C-AN, PK50%+C-AN, PK25%+C-AN, and only C-AN in normal and calcareous soils. Results showed that C-AN and reduced PK fertilization (up to 75 or 50%) increased photosynthetic pigments and promoted nutrient acquisition in quinoa grown in calcareous soil. Reduced PK fertilization to 75 or 50% plus C-AN in calcareous soil increased osmoprotectants, nonenzymatic antioxidants, and DPPH scavenging activity of quinoa’s leaves compared to the PK0%+C-AN treatment. The integrative application of high PK levels and C-AN enhanced the quinoa’s seed nutritional quality (i.e., lipids, carbohydrates, mineral contents, total phenolics, total flavonoids, half maximal inhibitory concentration, and antiradical power) in calcareous soil. At reduced PK fertilization (up to 75 or 50%), application of compost with Aspergillus niger through soil drenching increased plant dry weight by 38.7 or 53.2%, hectoliter weight by 3.0 or 2.4%, seed yield by 49.1 or 39.5%, and biological yield by 43.4 or 33.6%, respectively, compared to PK0%+C-AN in calcareous soil. The highest P-solubilizing microorganism’s population was found at PK0%+C-AN in calcareous soil, while the highest Azotobacter sp. population was observed under high PK levels + C-AN in normal soil. Our study recommends that compost with Aspergillus niger as a bioorganic fertilization treatment can partially substitute PK fertilization and boost quinoa’s tolerance to salt calcareous-affected soil.