Phosphorus (P) and potassium (K) have been well documented as key essential nutrients to increase alfalfa (Medicago sativa L.) production. However, other interrelated factors including cultivar, harvesting schedules, and relative levels of soil K, calcium (Ca), and magnesium (Mg) can influence response of alfalfa to P and K. With the current increasing trend of fertilizer prices and under conditions of nutrient availability and uptake, productivity and profitability of alfalfa in response to P and K applications is yet to be further explored. Five different experiments were conducted to (a) determine the influence of K, cultivar, and harvest time on productivity of new alfalfa stands, (b) evaluate K and harvest time effects on forage production of old alfalfa stands, (c) investigate the impacts of P and K in association with Ca and Mg, and harvest management on alfalfa, (d) ascertain the impacts of P and K in combinations with Ca and Mg, and harvest management on alfalfa under controlled environments, and (e) assess the economic returns of P, K, Ca, and Mg fertilization on alfalfa under different harvest systems. Treatments were (a) Field study one: four K rates (0, 56, 112, and 168 kg K2O ha−1), two cultivars (“Hi-Gest 360”; “AFX 457”), and two harvest times (early harvest, late bud to early [10%] bloom; late harvest, 7 days after early harvest) with four replications, (b) Field study two: six K rates (0, 56, 112, 168, 224, and 280 kg K2O ha−1) and two harvest times (early harvest, late bud to early [10%] bloom; late harvest, 7 days after early harvest) with four replications, (c) Field study three: 18 selected combinations rates of three P (0, 34, and 67 kg P2O5 ha−1), three K (0, 168, and 336 kg K2O ha−1), two Ca (0 and 560 kg CaO ha−1), and two Mg (0 and 56 kg MgO ha−1); and two harvest times (early harvest, late bud to early [10%] bloom; late harvest, 7 days after early harvest) with three replications; and (d) Greenhouse study: six selected combinations rates of two P (0 and 67 kg P2O5 ha−1), two K (0 and 336 kg K2O ha−1), three Ca (0, 4483, and 8967 kg CaO ha−1), and three Mg (0, 448, and 897 kg MgO ha−1); and two harvest times (early harvest [30 to 40 growth days], late harvest [7 days after early harvest]) with five replications. For each study, the respective treatments were organized in factorial arrangement in a randomized complete block design. For new alfalfa stands, there was a linear (P