Members of Mononegavirales, the order that includes nonsegmented negative sense RNA viruses (NNSVs), encode a small number of multifunctional proteins. In members of the Filoviridae family, virus protein 35 (VP35) facilitates immune evasion and functions as an obligatory cofactor for viral RNA synthesis. VP35 functions in a manner orthologous to that of phosphoproteins from other NNSVs. Although the critical roles of Ebola viral VP35 (eVP35) in immune evasion and RNA synthesis are well-appreciated, a complete understanding of its organization and its role in carrying out its many functions has yet to be fully realized. In particular, we currently lack information about the role of the oligomerization domain within eVP35. To address this limitation, we report here an investigation of the oligomer structure of eVP35 using hybrid methods that include multiangle light scattering, small-angle X-ray scattering, and cross-linking coupled with mass spectrometry to determine the shape and orientation of the eVP35 oligomer. Our integrative results are consistent with a parallel tetramer in which the N-terminal regions that are required for RNA synthesis are all oriented in the same direction. Furthermore, these results define a framework for targeting the symmetric tetramer for structure-based antiviral discovery.