Cellular proteomes are thought to be optimized for function, leaving no room for proteome plasticity and, thus, evolution. However, hybrid animals that result from a viable cross of two different species harbor hybrid proteomes of unknown complexity. We charted the hybrid proteome of a viable cross between Drosophila melanogaster females and Drosophila simulans males with bottom-up proteomics. Developing hybrids harbored 20% novel proteins in addition to proteins that were also present in either parental species. In contrast, adult hybrids and developmentally failing embryos of the reciprocal cross showed less additional proteins (5 and 6%, respectively). High levels of heat shock proteins, proteasome-associated proteins, and proteasomal subunits indicated that proteostasis sustains the expanded complexity of the proteome in developing hybrids. We conclude that increased proteostasis gives way to proteomic plasticity and thus opens up additional space for rapid phenotypic variation during embryonic development.