Objective: To investigate and compare knowledge, attitudes, and practices regarding pharmacovigilance (PV) and the reporting of adverse drug reactions (ADR) among physicians and pharmacists in primary care settings. Subjects and Methods: A cross-sectional study was conducted, in which a validated self-administered questionnaire was distributed to 386 physicians and 197 pharmacists in 38 primary care clinics in Kuwait. Categorical variables were described using numbers and percentages. The Pearson χ² test, Fisher exact test, and Mann-Whitney U test were used as appropriate. p < 0.05 was considered statistically significant. Results: Of the 583 questionnaires distributed, 485 were completed (by 318 physicians and 167 pharmacists), giving an overall response rate of 83.2%. A total of 52.8% (n = 256) and 70.5% (n = 341) of the study participants were knowledgeable about the definitions of PV and ADR, respectively, with pharmacists demonstrating significantly better knowledge of PV (n = 105/167 vs. 151/318, i.e., 62.9 vs. 47.5%; p < 0.001) and purpose (n = 123/167 vs. 177/318, i.e., 74.1 vs. 55.7%; p < 0.001). However, the majority (n = 434/485; 89.4%) were not aware of an ADR reporting system in Kuwait. Almost every participant (n = 474/485; 97.7%) thought it was necessary to report ADR. However, significantly fewer physicians than pharmacists (n = 248/318 vs. 147/167, i.e., 78.0 vs. 88.0%; p < 0.01) believed that ADR reporting was a professional obligation. Only 27.8% (n = 133/485) had reported ADR, with pharmacists having reported significantly fewer than physicians (n = 35/167 vs. 98/318, i.e., 21.7 vs. 30.8%; p = 0.036). Conclusions: This study indicated that the attitude was positive but there was suboptimal knowledge and poor practice among primary care physicians and pharmacists with regard to ADR reporting. Targeted training about ADR reporting while ensuring a robust regulatory framework would encourage ADR reporting practices in the primary health care setting in Kuwait.