Abstract Background Nomophobia is a psychological condition caused by a fear of disconnecting from others through mobile phones. Aim This study aims to determine the prevalence of and predictors of nomophobia and anxiety symptoms among the general population in Saudi Arabia and Jordan. Methods This study was an observational cross-sectional study using a web-based online survey distributed in two middle eastern countries (Saudi Arabia and Jordan) between Jun 24 and Jul 20, 2021. A convenience sample was used to recruit the study participants. Categorical variables were identified as frequencies and percentages. In addition, a binary logistic regression analysis was used to determine the factors associated with nomophobia symptoms. The Statistical Package for Social Science (SPSS) software, version 27 (IBM Corp, Armonk, NY, USA), analyzed the data. Results A total of 5,191 responded to the online survey. Around (26.5%) reported that they suffer from an anxiety problem or use a treatment for anxiety. The median daily time spent using a mobile phone (IQR) (minutes) was around 210 min per day. About half of the study sample (51.2%) are diagnosed with dependence syndrome. The binary logistic regression analysis revealed that those within the age group of 30–49 years and 50 years and above) are less likely to have mobile phone dependence compared to those less than 30 years old. Females were 16% at lower risk of developing mobile phone dependence compared to males Married participants were less likely to have mobile phone dependence compared to single participants (OR: 0.62 (95% CI 0.56–0.70)), while divorced participants were at a 46% higher risk of developing mobile phone dependence. Conclusion Nomophobia prevalence among Saudi Arabia and Jordon's population is 51.2%. Several factors may predict mobile phone dependence including age, gender, marital status, and previous history of anxiety.