Objective Estimate the prevalence of depression among individuals with a dry eye disease (DED) in Saudi Arabia using two questionnaires: Patient Health Questionnaire (PHQ-9) and Dry Eye Questionnaire (DEQ-5), and explore potential factors implicated in the development of depression among the DED population. Methods This is a descriptive cross-sectional study of 476 patients with DED which was conducted using a PHQ-9 questionnaire to screen for depression and a DEQ-5 questionnaire to diagnose DED. The questionnaires were merged and distributed using Google Forms through various social media platforms targeting the Saudi population. After data collection, it was revised, coded and fed to statistical software IBM SPSS version 22 (SPSS, Inc. Chicago, IL). Results Depression was diagnosed among 200 participants (42%) of the cases with dry eyes. From which 5.7% had mild depression, 13.9% had moderate depression, 12.6% had moderately severe depression, and 9.9% had severe depression. A female predominance was noticed; 44.7% of the females with dry eyes had depression compared to 32.4% of males with recorded statistical significance (P=0.023). Depression was detected among 55% of those who are less than 20 years old in comparison to 27% of those who are 30 years or older (P=0.001). Laser-assisted in-situ keratomileusis (LASIK), prolonged electronic device usage and contact lens wear are reported as risk factors associated with an increase in dry eye symptoms. However, there is no statistically significant relationship between contact lens wear and depression among dry eye disease patients. Conclusion Suffering from DED is a possible risk factor for developing depression as DED is associated with depression of higher degrees of severity. Depression among DED patients is found to be significantly more prevalent among females and the young adult population rather than older adults.