We present a method for synthesizing N-benzyl pyridones from para-quinone methides (p-QMs) and 2- or 4-hydroxy pyridines in the presence of a base at room temperature. The reaction proceeds through 1,6-Michael addition reaction. Simple operation, good to excellent yields, broad substrate scope, and good functional group tolerance are the salient features of the developed methodology. The synthesized N-benzyl pyridones displayed significant in vitro blood-stage antiplasmodial activity at sub-micromolar concentration.