The objects of programming semantics, namely, programs and languages, are inherently formal, but the derivation of semantic theories is all too often informal, deprived of the benefits of formal calculation “guided by the shape of the formulas.” Therefore, the main goal of this article is to provide for the study of semantics an approach with the same convenience and power of discovery that calculus has given for many years to applied mathematics, physics, and engineering. The approach uses functional predicate calculus and concrete generic functionals ; in fact, a small part suffices. Application to a semantic theory proceeds by describing program behavior in the simplest possible way, namely by program equations , and discovering the axioms of the theory as theorems by calculation. This is shown in outline for a few theories, and in detail for axiomatic semantics, fulfilling a second goal of this article. Indeed, a chafing problem with classical axiomatic semantics is that some axioms are unintuitive at first, and that justifications via denotational semantics are too elaborate to be satisfactory. Derivation provides more transparency. Calculation of formulas for ante- and postconditions is shown in general, and for the major language constructs in particular. A basic problem reported in the literature, whereby relations are inadequate for handling nondeterminacy and termination, is solved here through appropriately defined program equations. Several variants and an example in mathematical analysis are also presented. One conclusion is that formal calculation with quantifiers is one of the most important elements for unifying continuous and discrete mathematics in general, and traditional engineering with computing science, in particular.