Downregulation of protein phosphatase Cdc25 activity is linked to remodelling of the cell cycle during the maternal-to-zygotic transition (MZT). Here, we present a structure-function analysis of Cdc25. We use chimeras to show that the N-terminus regions of Cdc25 and Cdc25 control their differential degradation dynamics. Deletion of different regions of Cdc25 reveals a putative domain involved in and required for its rapid degradation during the MZT. Notably, a very similar domain is present in Cdc25 and deletion of the DNA replication checkpoint results in similar dynamics of degradation of both Cdc25 and Cdc25. Finally, we show that Cdc25 degradation is delayed in embryos lacking the left arm of chromosome III. Thus, we propose a model for the differential regulation of Cdc25 at the MZT.