Smk1 is a meiosis-specific mitogen-activated protein kinase (MAPK) in yeast that controls spore differentiation. It is activated by a MAPK binding protein, Ssp2, upon completion of the meiotic divisions. The activation of Smk1 by Ssp2 is positively regulated by a meiosis-specific coactivator of the anaphase promoting complex (APC/C) E3 ubiquitin ligase, Ama1. Here, we identify Isc10 as an inhibitor that links APC/CAma1 to Smk1 activation. Isc10 and Smk1 form an inhibited complex during meiosis I (MI). Ssp2 is produced later in the program, and it forms a ternary complex with Isc10 and Smk1 during MII that is poised for activation. Upon completion of MII, Isc10 is ubiquitylated and degraded in an AMA1-dependent manner, thereby triggering the activation of Smk1 by Ssp2. Mutations that caused Ssp2 to be produced before MII, or isc10 mutations, modestly reduced the efficiency of spore differentiation whereas spores were nearly absent in the double mutant. These findings define a pathway that couples spore differentiation to the G0-like phase of the cell cycle.