Several studies have been conducted to investigate the barriers to implementing evidence-based practice (EBP) worldwide. In Saudi Arabia, a few studies were conducted in hospital and mental health settings, and no study has explored the topic in primary healthcare settings. This study aimed to examine the barriers perceived by primary healthcare nurses in implementing EBP. This study employed a correlational and cross-sectional design. A total of 284 nurses were surveyed using the BARRIERS scale. Regression analysis was performed to identify the effects of predictor variables on the four subscales. The overall raw score on the BARRIERS scale was 86.21 (standard deviation = 16.15). The highest mean score was reported in the organizational subscale, followed by the innovation and communication subscales, whereas the lowest mean score was reported in the adopter subscale. The findings showed that the three top-ranked barriers were: (1) results of the studies are not generalizable to nurses’ setting, (2) facilities are inadequate, and (3) physicians do not cooperate with the implementation. Findings showed that nurses encounter organizational-related barriers to a moderate extent and EBP implementation varies depending on gender, level of education, and job position. There is a need to create and implement educational interventions and programs to overcome the barriers to effective EBP implementation among primary healthcare nurses.