The Central Gneiss Belt in the Grenville Province, Ontario, exposes metaplutonic rocks, orthogneisses, and minor paragneisses that were deformed and metamorphosed at crustal depths of 20–35 km during the Mesoproterozoic Grenvillian orogeny. We present sensitive high-resolution ion microprobe (SHRIMP) U–Pb zircon data from eight samples of migmatitic orthogneiss, granite, and pegmatite from the Muskoka and Shawanaga domains that constrain the age and duration of partial melting in the mid orogenic crust. Our results support earlier interpretations that the protoliths to these migmatitic orthogneisses formed at ca. 1450 Ma. Emplacement and crystallization of granite and pegmatite in the Shawanaga domain took place at ca. 1089 Ma, apparently coevally with deformation and high-grade metamorphism. Leucosomes in the Muskoka and Shawanaga domains yield ages of 1067 and 1047 Ma, respectively, interpreted as the ages of melt crystallization. The geochronological data and field observations suggest that melt was present at the mid-crustal level of the Grenville orogen during a significant part of its deformational history, probably at least 20–30 million years. By analogy with modern orogens, the amount and duration of melting observed in the Muskoka and Shawanaga domains may have had an impact on the orogenic evolution of the area.