Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic henipaviruses (HNVs) with case fatality rates between 50-100%. Currently, there are no approved human vaccines or antiviral treatments. Both NiV and HeV make use of a receptor binding protein (RBP) and fusion glycoprotein (F) to mediate entry into host cells. As such, both RBP and F are major targets in both vaccine designs and therapeutic development. Here, we report on a first-in-class camelid nanobody, DS90, that engages a unique, conserved site within prefusion F of NiV and HeV. Dimeric DS90 provided ultrapotent neutralization of both NiV and HeV and complete protection from NiV disease. Through cryogenic electron microscopy, we demonstrated that DS90 binds a quaternary pocket within NiV F, and blocks a site previously shown to be involved in F dimer-of-trimer assembly that is necessary for viral membrane fusion. As RNA viruses, HNVs are prone to immune escape under selection pressure. To address this, we combined DS90 with an anti-RBP antibody, m102.4, to deliver a dual-targeting biologic that is resistant to viral escape. Bispecific engineering of DS90 with m102.4 resulted in synergistic neutralization, elimination of viral escape and superior protection from NiV disease compared to leading monovalent approaches. Together, our findings provide proof-of-concept for the use of nanobodies to treat HNVs. Moreover, our results carry implications for the development of cross-neutralizing immunotherapies that limit the emergence of henipaviral escape mutants.