The interaction between phosphorus (P) and potassium (K) significantly influences alfalfa (Medicago sativa L.) production. However, our understanding of this interaction in soils with high levels of exchangeable K, calcium (Ca), and magnesium (Mg) remains limited. The interplay between soil P, K, Ca, and Mg, along with harvest timing, can affect the availability and uptake of P and K, leading to varied yield responses. Field research was conducted at the University of Wyoming James C. Hageman Sustainable Agriculture Research and Extension Center at Lingle, WY, to investigate this complex interaction and its impact on alfalfa production from 2019 to 2021. Treatments included (i) 18 selected combinations (kg ha−1) of three levels of P (0, 34, and 67 P2O5), three levels of K (0, 168, and 336 K2O), two levels of Ca (0 and 560 CaO), and two levels of Mg (0 and 56 MgO); and (ii) two harvest schedules (early harvest, late bud to early [10%] bloom; late harvest, 7–10 days after early harvest [∼100% bloom]). Treatments were factorially (18 × 2) arranged in randomized complete blocks with three replications. Under low levels of soil Ca and Mg, the 67 P2O5 and 336 K2O (kg ha−1 year−1) treatment produced the highest early harvest yield responses, while the 34 P2O5 and 336 K2O (kg ha−1 year−1) treatment excelled in late harvest yield. Alfalfa fertilized with 67 P2O5 and 336 K2O (kg ha−1 year−1) consistently achieved significant late harvest yield response in soils with high levels of Ca and Mg, leading to profitable forage production. Similar trends in P and K uptake were observed, indicating that fertilizing alfalfa with P and K can enhance productivity and profits even in soils rich in K, Ca, and Mg levels. In Wyoming and similar regions, we recommend that alfalfa growers and stakeholders consider soil nutritional status—particularly the relative exchangeable levels of K, Ca, and Mg—and harvest timing to develop P and K fertility programs for sustainable production and profitability.