Cowpea bruchids, when challenged by a soybean cysteine protease inhibitor scN, reconfigure their major CmCP digestive proteases and recover normal feeding and development. Evidence previously indicated that insects selectively induced CmCPs from subfamily B, that were most efficient in autoprocessing and possessed not only high proteolytic but scN-degrading activity. However, dietary scN only marginally increased genes from the more predominant CmCP subfamily A that were inferior to subfamily B in these regards. To gain further molecular insight into this adaptive adjustment, we initiated domain swapping between the two respective subfamily members B1 and A16, the latter unable to autoprocess nor degrade scN once transactivated. Swapping the propeptides did not qualitatively alter autoprocessing in either protease isoform. However, swapping a domain leading to four amino acid changes in A16 mature protein region upstream of C-25 (pAmBA) was sufficient to activate propeptide removal. Replacement of these amino acid residues to the corresponding B1 residues, singly and pair wise, revealed that activation of autoprocessing in pAmBA resulted from cumulative and/or coordinated individual effects. Bacterially expressed propeptides (pA16 and pB1) differed in their ability to inhibit B1 mature enzyme. Lower inhibitory activity in pB1 is likely attributable to its lack of protein stability. This instability in the propeptide is necessary, although insufficient by itself, for scN-degradation by its mature enzyme. Taken together, cowpea bruchids modulate proteolysis of its digestive enzymes by controlling propeptide maturation and stability, which explains at least in part the plasticity cowpea bruchids demonstrate in response to protease inhibitors.