Gastroesophageal reflux disease (GERD) symptom is a relapsing chronic medical condition resulting from the reflux of gastric acid contents into the esophagus and throat or mouth. It interferes with social functioning, sleep, productivity, and quality of life. Despite this, the magnitude of GERD symptoms is not known in Ethiopia. Therefore, this study was conducted to determine the prevalence and associated factors of GERD symptoms among university students in the Amhara national regional state. An institutional-based cross-sectional study was employed in Amhara national regional state Universities, from April 1, 2021, to May 1, 2021. Eight hundred and forty-six students were included in the study. A stratified multistage sampling technique was employed. Data were collected by using a pretested self-administered questionnaire. Data were entered via Epi Data version 4.6.0.5 and analyzed by SPSS version-26 software. The bivariable and multivariable binary logistic regression analyses were used to determine the associated factors of GERD symptoms. The adjusted odds ratio (AOR) with a 95% confidence interval (CI) was calculated. Variables having a p-value of ≤ 0.05 were considered statistically significant. The prevalence of GERD symptoms in this study was 32.1% (95% CI = 28.7-35.5%). Being in the age of 20-25 years (AOR = 1.74, 95%CI = 1.03-2.94), female (AOR = 1.67, 95% CI = 1.15-2.41), use of antipain (AOR = 2.47, 95% CI = 1.65-3.69) and soft drinks (AOR = 1.58, 95% CI = 1.13-2.20) were significantly associated with higher odds of GERD symptoms. Urban dwellers had less chance of having GERD symptoms (AOR = 0.67, 95% CI = 0.48-0.94). Nearly one-third of university students are affected by GERD symptoms. Age, sex, residence, use of antipain, and consumption of soft drinks were significantly associated with GERD. Reducing modifiable risk factors such as antipain use and soft drink consumption among students is advisable to decrease the disease burden.