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Background: Problematic internet use (PIU) or internet addiction has become increasingly prevalent, and concerns about its impact on mental health and social functioning have grown. This study aimed to investigate the prevalence of PIU among Syrian university students and its relationship with their demographics, internet user behavior, and mental health. Methods: A cross-sectional study was conducted among undergraduate medical students in Syrian government universities between 12 April and 29 May 2022. The survey included the Beck Depression Inventory and the Internet Addiction Scale. Results: Out of 2891 participants, 75.2% were female, with an average age of 21.87. The average Internet Addiction Test (IAT) score was 49.4, and the overall prevalence of PIU was 89%. Furthermore, 93.0% of participants displayed possible signs and symptoms of depression. PIU was significantly linked with physical abuse (p = 0.001) and mental stress (p = 0.0001). Internet addiction is (AOR:1.723, COR:2.289) fold more likely to occur in those with more than 8 h of sleep per night than in those who sleep for less than 6 h (p-value < 0.05). Unadjusted regression analysis showed that 13 predictors of the independent variables were statistically significant in predicting the presence of internet addiction, such as participants who suffered from a breakup (COR:2.039), domestic violence (COR:2.136), physical abuse (COR:2.190), or mental stress (COR:2.621) were more likely to be affected by internet addiction than those who did not (p-value < 0.05). Conclusions: The study found a high rate of internet addiction among Syrian medical students, with those experiencing mental health problems and depression symptoms more likely to be internet addicts. To prevent PIU, students should be encouraged to participate in extracurricular activities, such as sports, and awareness programs should be enhanced to highlight the negative effects of internet addiction.