Excessive smartphone use leads to several physical and psychological disorders, particularly among young adults. This study aimed to investigate the prevalence and the associated factors of problematic smartphone use (PSU) among health sciences students in Jeddah, Saudi Arabia. During the 2019 academic year, a cross-sectional analytic study randomly recruited 408 health sciences students (67.5% were females), with a mean age of 20.5 ± 1.42. Data on sociodemographic and health profiles, smartphone usage patterns, and overuse symptoms were collected for each participant. The Smartphone Addiction Scale-Short Version (SAS-SV) and Generalized Anxiety Disorder 7-item (GAD-7) scale were used to assess PSU and anxiety levels. PSU was detected in 66.9% of the study participants. The prevalence is high among both females and males (69.5 and 61.7%, respectively). PSU was found to be associated with more years of use and frequent smartphone upgrading (aOR = 2.11, 95% CI: 1.12, 3.97) and (aOR = 1.69, 95% CI: 1.08, 2.65), respectively (p = 0.021 and 0.021, respectively). Participants with moderate and severe anxiety levels were found to be more likely to have PSU (aOR = 2.22, 95% CI: 1.21, 4.05) and (aOR = 5.97, 95% CI: 2.41, 14.78), respectively. (p = 0.010 and < 0.001, respectively). PSU is an emerging problem among health sciences students in Saudi Arabia with a high prevalence in both genders. Longer years of use, more frequent smartphone upgrades, and higher anxiety levels are associated with PSU among health sciences students. Special health education and psychological support programs are recommended to guide and support future healthcare providers against the consequences of PSU.