Sales and marketing personnel are among the most knowledgeable individuals regarding the safety of the medications they promote. No previous work has assessed pharmaceutical sales and marketing personnel’s knowledge, attitude, practice (KAP), and barriers toward pharmacovigilance (PV) in Saudi Arabia; therefore, the present study aimed to assess these aspects and to scrutinize their associations with the subjects’ baseline characteristics. A validated questionnaire comprising five sections (baseline characteristics, knowledge, attitude, practice, and barriers) was disseminated via email networks and social media platforms between 18 March and 31 May 2025. All employees working in the sales and marketing departments of pharmaceutical companies in Saudi Arabia were eligible to participate. Participants’ responses were categorized as good or poor knowledge, positive or negative attitude, good or poor practice, and challenging or non-challenging work environment, based on the cumulative score in each respective section, using a 60% cutoff. A total of 400 participants completed the survey. Of these, about one-third (37.3%) had 2–4 years of professional experience and two-thirds (63%) were employed by multinational companies. Overall, 57% and 83.5% had good knowledge and positive attitude, respectively. The work environment was considered non-challenging by 92.8% of participants, and 61% reported good practice. We noted that holding a non-pharmacy degree was a significant predictor of poor knowledge and a challenging work environment. Additionally, employment in a local company was significantly associated with poor knowledge and practice. Pharmaceutical sales and marketing personnel in Saudi Arabia demonstrated acceptable levels of KAP and reported few barriers toward PV, with an opportunity for improvement.