Protein expression is maintained through the regulation of both translation and proteolysis. Since levels of degradation intermediates, i.e., partially degraded proteins, cannot be distinguished from those of stable proteins in global proteomics, which quantifies total protein levels, the mechanism underlying the regulation of protein degradation would be underrepresented using only global proteomics approaches. This study aimed to assess the unclear aspects of degradational regulation through a new multiplexed N-terminomics method involving selective isobaric labeling on protein N-termini and immunoaffinity capture of the labeled N-terminal peptides. Our method allows for not only identification of proteolytic cleavage sites, but also highly multiplexed quantification of degradation intermediates, enabling time-resolved profiling of protein degradation. The present method uniquely highlights the regulation of proteomic degradation rate during early embryogenesis in Drosophila melanogaster; furthermore, our method revealed that a group of zygotically expressed proteins are also expressed during embryogenesis but were stringently regulated through active degradation to maintain baseline expression levels.