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Introduction: Adverse childhood experiences (ACEs) are widely prevalent and interrelated. They affect multiple domains of health while having a dose-response effect. These effects are biologically plausible, where ACEs are found to be highly associated with physical and mental comorbidities., Objectives: The study aimed to measure the magnitude of ACE and its relationship to mental and physical illnesses in the Eastern Region of Saudi Arabia by assessing its prevalence., Materials and Methods: This was a retrospective cohort study that took place in the Eastern Region of Saudi Arabia in 2020., Setting: It was applied to a population-based, random adult sample from both genders, different educational levels and socioeconomic statuses., Participants: Those who were 19 years old and above and living in the Eastern region were included. Everyone under the age of 19, those not currently living in the Eastern Region, and those who did not complete the questionnaire were excluded., Results: The total sample size was 611 respondents, but after applying the exclusion criteria, 507 respondents were included. Most participants were females (65.1%). The mean age of the participants was 29.7 years, with a standard deviation of 11.2 years. Regarding educational level, 69.6% were college/university graduates. Most study respondents (81.8%) were exposed to four or more types of ACEs, with emotional neglect being the most common type (82.2%). Having four or more ACEs increases the risk of having physical illnesses compared to those with only one. Furthermore, female respondents who had four or more ACEs had the highest likelihood of having depressed mood (Adjusted odds ratio [AOR] = 1.04; 95% confidence interval [CI] = 1.0-1.07), stress (AOR = 2.8; 95% CI = 1.11-7.3), and insomnia (AOR = 1.04, 95% CI = 1.01-1.07)., Conclusion: Our study showed that in the Eastern Region, ACEs are highly prevalent and are associated with an increased risk of mental and physical illness., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)