The evidence-based practice of primary care physicians is essential because they are the first line of contact with the local community, and they cater to most of their communities’ health needs. In the current study, in which we used a cross-sectional survey in northern Saudi Arabia, we assessed primary care physicians’ knowledge, attitude, practice, and barriers regarding evidence-based medicine (EBM). Of the 300 physicians who participated, less than half had high knowledge (43.7%) and attitude (47.7%) toward EBM. The chi-square test revealed that the knowledge categories were significantly associated with the age group (p = 0.002) and EBM training received in the past five years (p < 0.001), and the attitude categories were significantly associated with nationality (p = 0.008). Of the respondents, 155 (51.7%) used EBM in their daily clinical practice. Through logistic regression analysis, we found that the identified predictors of including EBM in clinical practice were the 31–45-year-old age group (adjusted odds ratio (AOR) = 2.11, 95% confidence interval (CI) = 1.65–2.73) and EBM training received during last 5 years (AOR = 2.12, 95% CI = 1.35–2.94). We recommend enhancing primary care physicians’ knowledge of EBM and its importance in clinical practice through appropriate training programs. A multi-centric mixed-method survey is warranted in other provinces of the KSA to recognize region-specific training demand.