Background Medication errors pose a risk for individual patients and for public health, with the misuse and overuse of medications being linked to severe patient safety problems. Therefore, the objective of this study was to investigate healthcare professionals’ (HCPs’) knowledge about medication errors, their knowledge about medication error reporting systems, and predictors for HCPs to report medication errors in Saudi Arabia. Methods An observational cross-sectional study was conducted among HCPs (physicians, pharmacists, and nurses) between January and March 2020. The study included 6 distinct locations in the Saudi Arabian regions of Hail, Al-Qassim, Al-Jouf, Al-Madinah, the eastern region, and the western region. Descriptive statistical and inferential analyses were computed using Statistical Package for the Social Sciences (SPSS) v.22. Results In total, 980 questionnaires for 348 (35.5%) physicians, 144 (14.7%) pharmacists, and 488 (49.8%) nurses were distributed with a response rate of 100%. Interestingly, only 277 (28.3%) of the HCPs had a good understanding of the stages of medication errors. With regard to reporting practices, a high number of the HCPs, 576 (58.8%), had not reported medication errors in their workplaces, and nearly 369 (37.7%) of respondents said they believe that legal implications are a major barrier to the reporting of medication errors. More than half, 524 (53.5%), of HCPs revealed that no clear electronic system is available for the reporting of medication errors in most hospitals. In addition, 537 (54.8%), of the HCPs had not attended any training programs regarding medication error reporting systems within the past year, which is alarming. Conclusion Our study identified a huge lack of the reporting of medication errors, knowledge about medication error stages, and training on medication errors. Therefore, an urgent need to address these weaknesses exists.