BACKGROUND: Smartphone addiction is an emerging type of addiction in the digital era, characterized by smartphone dependence that negatively affects human health with a wide range of psychological and physical manifestations. OBJECTIVE: This study aimed to evaluate the detailed clinical manifestations of smartphone addiction as a delineated clinical syndrome. METHODS: A cross-sectional study design was employed to assess smartphone addiction prevalence and its health impacts among Syrian undergraduates using the Smartphone Addiction Scale-Short Version (SAS-SV 2013), the Kessler psychological distress scale (K-6), and a comprehensive assessment of the clinical manifestations frequently linked to smartphone addiction in the literature. Different statistical modeling techniques were applied; a value of < .05 was considered statistically significant. RESULTS: Of 1532 invited undergraduates, 1401 (91.45%) completed the assessment adequately. Most participants were females (59.7%) and below 23 years of age (73.2%). The prevalence of smartphone addiction was 67.80%; statistically significant smartphone addiction associations were revealed with psychological distress ( < .0001) with odds ratios of 3.308. Most screened physical manifestations also showed a significant association with smartphone addiction. CONCLUSION: A high prevalence of smartphone addiction was observed with a broad spectrum of associated mental and physical manifestations. As smart device addiction becomes a global health concern, combining the clinical findings reported in the related literature into one clinical identity is necessary to develop a holistic management approach for the delineated clinical syndrome.