Nd-Sr-Pb isotope data are used to characterize the sources of Late Neoproterozoic and Early Paleozoic siliciclastic rocks of the Teplá-Barrandian unit of the Bohemian Massif. Geochemical and isotopic signatures of samples from different stratigraphic levels reflect changing sources and weathering conditions through time and allow a correlation with shifting geotectonic regimes. Late Neoproterozoic rocks were deposited in a magmatic arc–related setting within the Avalonian-Cadomian belt at the periphery of West Gondwana. Fine-grained graywackes yield crustal residence ages (T_DM) of 2.17–1.49 Ga, documenting contributions of old crust. Their ϵNd₅₇₀ values, as well as Pb and Sr isotopic compositions, reflect mixing of detritus derived from old crust with a Neoproterozoic magmatic arc component. The change in the geo-tectonic regime to transtension/rifting occurred during the terminal Neoproterozoic and is documented by more radiogenic ϵNd_T values (−6.0 to +1.0) and younger T_DM (1.65–1.12 Ga) of the Cambrian sediments. Besides the involvement of a post-Neoproterozoic juvenile source, the Lower Cambrian basin was also fed from an old upper crustal domain, as indicated by their high ²⁰⁷Pb/²⁰⁶Pb values. In contrast, Middle Cambrian siliciclastic rocks are mainly derived from the Cadomian basement. In the Ordovician pelites, ϵNd_T values of −9.6 to −8.3 and radiogenic Sr and Pb isotopic compositions reflect an increasing input of material derived from the cratonic hinterland. Their T_DM values range from 2.02 to 1.88 Ga. The uniform geochemical and isotopic compositions of the Ordovician samples indicate efficient mixing of the detritus prior to deposition in a mature rift or shelf environment at the Gondwanan margin.