The biogeography and faunal evolution of middle to late Eocene mammals throughout East Asia is assessed. Appearance Event Ordination was used to get a reliable temporal ordination of 92 Paleogene faunas from East Asia. Results from this analysis are generally consistent with the faunal sequence of traditional East Asian Land Mammal “Ages” (EALMAs). Exceptions are that the Arshantan Fauna fell within Irdinmanhan EALMA faunas, and three latest middle to late Eocene faunas from southern East Asia are misaligned due to high degrees of endemism. Comparison of 30 major middle/late Eocene mammalian faunas at the generic level, using Simpson's Faunal Resemblance Index and the ordinal composition of each fauna indicate that: (1) the differentiation in faunal similarity and composition between northern and southern East Asia started near the middle Eocene-late Eocene boundary; (2) this differentiation is reflected by the decline of perissodactyls and radiation of several artiodactyl clades in the later Eocene of southern East Asia; and (3) in southern East Asia, faunal endemism increased in the later Eocene. The latest middle to late Eocene faunas of the southern area do not fit within the EALMA system, which was primarily established with northern faunas, because of their endemism. Mammalian faunal changes actually seem to have begun much earlier in the southern region of East Asia than in the northern part, so the faunal changes toward the end of the Eocene in East Asia were not synchronous. Faunal changes during the Eocene-Oligocene transition in southern East Asia seem not to have been controlled by global climatic changes.