The warmest global temperatures of the Cenozoic Era occurred in early Eocene time, following a warming trend that started in late Paleocene time. The greater Green River Basin of southwestern Wyoming is one of the best areas in the Rocky Mountains for paleobotanical investigation of the Paleocene-Eocene climatic transition. Intensive sampling has resulted in the recovery of an estimated 189 species of plant macrofossils from the Tiffanian, Clarkforkian, Wasatchian, and Bridgerian land mammal “ages.” The leaf morphologies and taxonomic affinities of these fossils were used in combination with other indicators to evaluate Paleocene-Eocene climates. Following cool humid conditions in the Tiffanian, the Clarkforkian was humid and subtropical, and several plant families with modern tropical affinities appeared. However, as in the Tiffanian, Clarkforkian floras had low diversity and were dominated by a single species in the birch family. Mean annual temperature (MAT) rose from an estimated 12 °C in the Tiffanian to 19 °C in the Clarkforkian, while mean annual precipitation (MAP) for the Tiffanian and Clarkforkian is estimated to have been 130–150 cm. Little fossil plant material is preserved from the latest Clarkforkian or the earliest Wasatchian, which is thought to have contained an interval of cooling and drying followed by renewed warming. By the middle Wasatchian, the time of the Cenozoic thermal maximum, the inferred MAT was about 21 °C, and the MAP was near 140 cm. A second influx of plant families with tropical affinities appeared in the area, and diversity increased significantly, but most plant families known from the Clarkforkian persisted. Species turnover from the Clarkforkian to the Wasatchian was greater than 80%. A second turnover of more than 80% of species (but not families) from the Wasatchian to the early Bridgerian accompanied drying and increased seasonality of precipitation. The early Bridgerian MAT is inferred to have been near 20 °C and the MAP to have been about 80 cm. Except for the Tiffanian and possibly portions of the early Wasatchian, paleoclimates during the study interval were predominantly frost free. Although the moderating influence of the Green River lake system has been suggested as a possible explanation for mild Eocene winters in Wyoming, this study shows that virtually frost-free climates existed in the area prior to and independent of significant lake development.