Background Burnout syndrome may adversely affect health care workers and health sciences students. The purpose of this study was to assess the prevalence of burnout among Saudi third- and fourth-year radiological sciences students across three campuses of King Saud bin Abdulaziz University for Health Sciences. Methods An exploratory, cross-sectional study was conducted among 176 Saudi radiological sciences students, using the Maslach Burnout Inventory-General Survey for Students. The 16-item questionnaire was administered electronically. The arithmetic means of individual items making up each scale of burnout were calculated, and statistical analyses were performed using Mann-Whitney U nonparametric test. Results From the 176 radiological sciences students approached, 96 (54.5%) completed the questionnaire. The percentage of students who were at moderate to high risk of burnout for emotional exhaustion, cynicism, and professional efficacy were 70.8%, 75% and 74%, respectively. Fourth-year students emotional exhaustion mean scale score was 19.3 ± 6.8 indicating significant higher burnout levels (P = 0.042), compared to third-year students mean scale score of 15.9 ± 7.2. Fourth-year female students cynicism mean scale score was 16.3 ± 7.6 indicating significant higher burnout levels (P = 0.035), compared to third-year female students mean scale score of 10.3 ± 7.1. Fourth-year female students showed significant lower professional efficacy mean score (21.1 ± 8.0), compared to males (26.1 ± 7.9, P = 0.007). Conclusions Our study shows 73.3% moderate to high burnout rates among Saudi radiological sciences students. A greater proportion of fourth year female students reported high levels of emotional exhaustion. Burnout increases as students advance to the fourth year. A block/modular curriculum structure for fourth-year courses may be necessary to reduce burnout among fourth-year students. The provision of academic counseling can relieve students' emotional stress and therefore reduce the risk of burnout.