Nipah virus and Hendra virus are highly pathogenic henipaviruses for which there are no approved therapeutics for use in humans. Using recombinant Cedar virus expressing luciferase (rCedV-Luc) as a CL2 surrogate, we screened a library of 2,703 Food and Drug Administration (FDA)-approved compounds, yielding 5 promising candidates: bortezomib, harringtonine, homoharringtonine, ixazomib citrate and lanatoside C. Compounds demonstrated low half-maximal inhibitory concentration (IC50) values of ≤0.45 µM and high selectivity indexes >6 in mammalian cell lines. Time-of-addition studies suggest that these compounds target a post-entry stage of henipavirus replication. This study demonstrates the utility of rCedV-Luc as a surrogate for the antiviral screening of henipaviruses and identification of promising candidates for further investigation and development as henipavirus antivirals.