The urocortin 1 (UCN1)-expressing neurons of the centrally projecting Edinger-Westphal nucleus (EWcp) are affected by the circadian rhythm, hormonal changes, stress and pain that are known to trigger migraine. Here we aimed at investigating the possible role of EWcp in migraine neurobiology.RNAscope in situ hybridization (ISH) combined with immunostaining was used to examine the expression of calcitonin gene-related peptide (CGRP) receptor component (Crcp) in both mouse and human EWcp and dorsal raphe nucleus (DRN). Anterograde and retrograde tracing study investigated the neuroanatomical connection between EWcp and the spinal trigeminal nucleus (STN). The functional connectivity matrix of Edinger-Westphal (EW) was examined using fMRI in humans. The CGRP injection model of migraine was applied and validated by light-dark box test in C57BL/6J mice then ISH combined with immunostaining was used to assess the functional and morphological changes.We proved the presence of Crcp mRNA in both murine and human DRN and EWcp. We identified a direct urocortinergic projection from EWcp to the STN. This was further supported by the strong positive functional connectivity between EW and STN as well as DRN in humans. Photophobic behavior along with increased FOS immunoreactivity in the lateral periaqueductal gray matter and trigeminal ganglia supported the efficacy of CGRP-induced migraine-like state. CGRP administration increased the Ucn1 mRNA expression, FOS and UCN1 peptide content of EWcp neurons. In the DRN both serotonin and tryptophan hydroxylase 2 levels were decreased.The presented data strongly suggests a possible neuromodulatory role of EWcp in the neurobiology of migraine.