Sedimentary sequences in the Columbia Plateau region of the Pacific Northwest ranging in age from 16-4 Ma contain fallout tuffs whose origins lie in volcanic centers of the Yellowstone hotspot in northwestern Nevada, eastern Oregon and the Snake River Plain in Idaho. Silicic volcanism began in the region contemporaneously with early eruptions of the Columbia River Basalt Group (CRBG), and the abundance of widespread fallout tuffs provides the opportunity to establish a tephrostratigrahic framework for the region. Sedimentary basins with volcaniclastic deposits also contain diverse assemblages of fauna and flora that were preserved during the Mid-Miocene Climatic Optimum, including Sucker Creek, Mascall, Latah, Virgin Valley and Trout Creek. Correlation of ashfall units establish that the lower Bully Creek Formation in eastern Oregon is contemporaneous with the Virgin Valley Formation, the Sucker Creek Formation, Oregon and Idaho, Trout Creek Formation, Oregon, and the Latah Formation in the Clearwater Embayment in Washington and Idaho. In addition, it can be established that the Trout Creek flora are younger than the Mascall and Latah flora. A tentative correlation of a fallout tuff from the Clarkia fossil beds, Idaho, with a pumice bed in the Bully Creek Formation places the remarkably well preserved Clarkia flora assemblage between the Mascall and Trout Creek flora. Large-volume supereruptions that originated between 11.8 and 10.1 Ma from the Bruneau-Jarbidge and Twin Falls volcanic centers of the Yellowstone hotspot in the central Snake River Plain deposited voluminous fallout tuffs in the Ellensberg Formation which forms sedimentary interbeds in the CRBG. These occurrences extend the known distribution of these fallout tuffs 500 km to the northwest of their source in the Snake River Plain. Heretofore, the distal products of these large eruptions had only been recognized to the east of their sources in the High Plains of Nebraska and Kansas.