The origins of high-silica igneous rocks are debated, as they may be products of high-degree fractional crystallization or low-degree partial melting. They may play a role in the generation of intermediate igneous rocks and are responsible for large, ash-rich volcanic eruptions. High-silica granites and rhyolites in the Sierra Nevada, California, and the Colorado Mineral Belt (CMB) are investigated using isotope geochemistry to better understand how they bear on these questions. Zircon U-Pb geochronology identifies two intrusive suites comprising large volumes of high-silica granites emplaced in the mid-Cretaceous Sierra Nevada batholith: the 106-98 Ma Shaver Intrusive Suite (SIS) in the central part of the batholith, and the 103-100 Ma Kearsarge intrusive suite (KIS) on the Sierra Crest and Owens Valley. High-silica granites in both suites have relatively high concentrations of middle rare earth and high field strength elements. Data for these and other discrete high-silica plutons in the batholith suggest they were derived from titanite-free sources in the deep crust, unlike similarly felsic parts of zoned intrusive suites. Despite similar trace element signatures, SIS and KIS high-silica granites have divergent isotopic compositions. High-silica granites of the SIS have supracrustal O in zircon, crustal Sr and Nd whole rock isotopic compositions, and negative Ce anomalies suggesting the SIS granites may have been derived from oceanic sedimentary sources. In contrast, KIS granites have mantle-like isotopic compositions. The location and geochemistry of the KIS suggests it may have resulted from backarc magmatism in the mid-Cretaceous Sierra. Volcanic and plutonic rocks in the central CMB were emplaced during the Laramide orogeny and subsequent Oligocene-Eocene volcanic flare-up. Strontium and Nd data suggest the 63-39 Ma Twin Lakes pluton and igneous rocks as young as 24 Ma were derived from a persistent mafic lower crust or enriched lithospheric mantle source. In contrast, the ~35 Ma Grizzly Peak Tuff and resurgent plutons are isotopically dissimilar from each other and the CMB as a whole, suggesting derivation by partial melting of ancient felsic lower crust. This distinct source could account for the lack Mo mineralization in the Grizzly Peak caldera relative to other high-silica parts of the CMB.Doctor of Philosoph