Bunyaviruses are segmented, single-stranded, negative-or-ambisense RNA viruses, including several zoonotic pathogens that are commonly transmitted by arthropod vectors, increasing the likelihood of outbreaks. Despite causing severe disease, virus-host interactions remain poorly characterised for many bunyaviruses, and few effective antivirals or vaccines exist against these viruses. Reflecting this, the World Health Organisation identified several bunyaviruses as priority pathogens for research. The bunyavirus Oropouche virus (OROV) frequently circulates in Central and South America and causes Oropouche fever, a febrile illness which can progress to encephalitis, meningitis, and death. Concerningly, there are ongoing outbreaks in Latin America with reports of infection-associated miscarriage, microcephaly, and death in previously healthy individuals. OROV was recently named as a priority pathogen by the UK Health Security Agency, highlighting an urgent need to further understand its lifecycle.  To provide new understanding of OROV, we conducted a whole cell proteomics screen of infected cells which revealed virus-induced depletion of several host proteins including RNA polymerase II (RNAPII). The non-structural protein NSs of several bunyaviruses is known to antagonise the interferon response by inhibiting RNAPII activity, although how OROV-NSs targets RNAPII remains unknown. We have now demonstrated OROV-NSs causes a potent dose-dependent inhibition of RNAPII-dependent transcription and have identified specific residues within OROV-NSs that are crucial for this activity. To investigate this further, we utilised immunoprecipitation pull-down mass spectrometry to identify interacting partners of OROV-NSs. These data further our understanding of OROV-host cell interactions, which could aid design of therapeutics to treat OROV infections.