Variable-rate (VR) application of inputs in South African cash crop production is mainly concerned with fertilizer and lime, and this indicates the importance of these inputs in cash crop production. However, the profitability of VR application of inputs has not yet been investigated under South African conditions. This paper studies the maize yield response to variable-rate application of phosphorus (P) and the profitability thereof in South Africa, on the basis of data collected on a 104-hectare experimental field on a farm in the Bothaville district. The strip-plot design of 180 strips was used for this on-farm research experiment. This design involved treatments that run in the same direction across the field as planting and harvesting. The objective is to determine the maize crop response functions under different P rates and to estimate the profitability of VR relative to the single-rate (SR) application of P. The methodology involves modelling maize yield response functions for P under VR and SR treatments, and for different management zones. A spatial quadratic regression model is developed, according to which yield is estimated as a function of applied P, the treatment and management zones. The results indicate that yield response to P varies between VR and the SR application methods, as well as between management zones. Variable-rate treatment results in higher profits than the SR treatment.