A pseudo-binary solid solution formed with two structurally dissimilar end members possesses a structural phase boundary, commonly called the morphotropic phase boundary (MPB). Many of the technologically useful piezoelectric oxides exhibit their maximum piezoelectric responses at a characteristic composition that corresponds to the MPB. Here we present a first-principles approach that can predict the existence of the MPB and its unique chemical composition. By evaluating the composition-dependent Kohn–Sham energy for both rhombohedral (R3c) and orthorhombic (Pbnm) phases, we have correctly reproduced the experimentally reported MPB compositions of two BiFeO3(BFO)-based multiferroics having a R3c–Pbnm phase boundary: x = 0.30 for La-modified BFO (Bi1−xLaxFeO3) and x = 0.14 for Sm-modified BFO (Bi1−xSmxFeO3). The present ab initio approach can be exploited as a useful guideline for the compositional design of ferroics having high piezoelectric responses.