We present the geologic history of the High Rock caldera complex (HRCC; Nevada, USA), a major mid-Miocene silicic center associated with flood basalt volcanism. Based on 70 40Ar/39Ar ages and new 1:24,000- and 1:100,000-scale geologic mapping, we document that between ca. 16.5 and 15.5 Ma a minimum of ∼700 km3 of rhyolitic magma erupted from the HRCC, covering an area of ∼8300 km2 in northwestern Nevada and southern Oregon (USA). The volcanism immediately followed eruption of the Steens flood basalt in the region, and was contemporaneous with eruption of compositionally similar rhyolites from the McDermitt volcanic field (MVF) to the east. The HRCC and MVF together mark the starting point for the eastward-younging trend of voluminous rhyolitic calderas of the Snake River Plain–Yellowstone trend. The HRCC comprises 4 major calderas, 24–40 km in diameter, that young from north-northeast to south-southwest: the Virgin Valley caldera formed on eruption of the 16.38 Ma high-silica alkali rhyolite Idaho Canyon Tuff; the overlapping Badger Mountain caldera collapsed due to eruption of the 16.34 Ma crystal-rich, low-silica rhyolite Summit Lake Tuff; eruption of the moderately peralkaline high-silica alkali rhyolite Soldier Meadow Tuff at 16 Ma resulted in formation of the Hanging Rock caldera; and the Cottonwood Creek caldera formed on eruption of the newly recognized, 15.70 Ma tuff of Yellow Rock Canyon, which is zoned from high-silica alkali rhyolite to trachyte. The four calderas contain caldera fill deposits, including pumice and ash falls, lahars, phreatomagmatic deposits, and well-bedded lacustrine deposits, which preserve diverse mid-Miocene fossil fauna and flora. Au and U mineralization developed along ring fractures of the Virgin Valley and Cottonwood Creek calderas. After silicic volcanism largely ceased, trachyte, trachyandesite, and alkalic basaltic lavas erupted through the caldera lakes. Intense silicic volcanism at the HRCC during the interval 16.4–15.5 Ma overlapped the eruption of the Steens and Columbia River Basalts, strongly suggesting a petrogenetic link. We propose that the HRCC and MVF caldera centers are localized where dikes of Steens flood basalt encountered transitional crust west of the craton with a composition and thickness that allowed significant partial melting, based on the O and Nd isotopic values of the rhyolites, which require involvement of crustal melts in their origin. Steens Basalt eruptions largely ceased in the area by the time the oldest caldera-forming ignimbrites erupted at both the HRCC and MVF, indicating that once large silicic magma bodies aggregated in the crust, they intercepted flood basalt dikes. We suggest that the roots of the HRCC and MVF are composed of large volumes of gabbroic intrusions and cumulates formed by fractional crystallization of HRCC magmas, which strengthened the middle crust beneath the calderas; major basin-bounding normal faults are diverted around them, but outflow ignimbrites are prominently offset by Basin and Range faults.