The onset of mountain building in the western part of the Himalayan orogenic belt has been documented in the synorogenic stratigraphic record of northern Pakistan and India as Early to Middle Eocene (52 Ma). Eocene strata in the Tethyan portion of the central part of the Himalayan orogenic belt consist of shallow marine carbonate rocks that lack evidence for initial Himalayan orogenesis, thus leaving open the possibility that the onset of orogeny was significantly diachronous along strike. We report U–Pb ages of detrital zircons and Nd-isotopic and trace element data from associated mudrocks in Cretaceous–Paleocene(?), Eocene, and lower Miocene strata of the southern Lesser Himalayan zone of central Nepal. The Cretaceous–Paleocene(?) Amile Formation is dominated by zircons with Archean–Early Proterozoic U–Pb ages. An abrupt influx of Cambrian–Ordovician and Middle to Late Proterozoic zircons marks the transition into the Eocene Bhainskati Formation, and indicates the onset of erosion of Tethyan rocks in the nascent Himalayan thrust belt. An increased proportion of Late Proterozoic zircons in fluvial litharenites of the lower Miocene Dumri Formation signals initial erosion of Greater Himalayan protoliths. The Nd-isotopic and trace element data support the unroofing history documented by the U–Pb zircon ages. The fact that middle Eocene strata in Nepal were derived from the Himalayan thrust belt reduces the maximum time lag between the onset of orogenesis in the northwest and central Himalaya to no more than 2 My.