Background The Full Outline of Unresponsiveness (FOUR) score is a clinical instrument for the assessment of consciousness which is gradually gaining ground in clinical practice, as it incorporates more complete neurological information than the Glasgow Coma Scale (GCS). The main objectives of the current study were the following: (1) translate and cross-culturally adapt the FOUR score into Greek; (2) evaluate its clinimetric properties, including interrater reliability, internal consistency, and construct validity; and (3) evaluate the reliability of assessments among health care professionals with different levels of experience and training. Methods The FOUR score was initially translated into Greek. Next, patients with neurosurgical pathologies in need of consciousness monitoring were independently assessed with the GCS and FOUR score within one hour by four raters who had different levels of experience and training (two board-certified neurosurgeons, a neurosurgery resident, and a registered nurse). Interrater reliability, internal consistency, and construct validity were evaluated for the scales using weighted Cohen’s κ ( κ w) and intraclass correlation coefficients (ICC), Cronbach’s α and Spearman’s ρ values, respectively. Results A total of 408 assessments were performed for 99 patients. The interrater reliability was excellent for both the FOUR score (ICC = 0.941) and GCS (ICC = 0.936). The values of κ w exceeded 0.90 for all pairs, suggesting that the FOUR score can be reliably applied by raters with varying experience. Among the scales’ components, FOUR score’s brainstem and respiratory items showed the lowest, yet high enough ( κ w > 0.60), level of agreement. The interrater reliability remained excellent ( κ w > 0.85, ICC > 0.90) for all diagnosis and age groups, with a trend toward higher FOUR score values in the most severe cases (ICC = 0.813 vs. 0.723). Both the FOUR score and GCS showed high internal consistency (Cronbach’s α > 0.70 for all occasions). The FOUR score correlated strongly with GCS (Spearman’s ρ > 0.90 for all raters), suggesting high construct validity. Conclusions The Greek version of the FOUR score is a valid and reliable tool for the clinical assessment of patients with disorders of consciousness. It can be applied successfully by nurses, residents, and specialized physicians. Therefore, its use by medical practitioners with different levels of experience and training is strongly encouraged. Supplementary Information The online version contains supplementary material available at 10.1007/s12028-021-01342-w.