Background: Medicines are intended to cure, prevent, or diagnose diseases, alleviate signs, or symptoms, but improper use can cause patient morbidity and even mortality. Pharmacists assume direct responsibility for all the patient’s drug-related needs. Hence, pharmacists’ knowledge and attitudes regarding pharmaceutical care (PC) and their perceived barriers to PC provision are imperative to treatment success. The aim of the study was to explore community pharmacists’ knowledge and perception towards pharmaceutical care and identifying perceived barriers towards its implementation in South Africa. Methods: A quantitative study was undertaken, using a descriptive cross-sectional design. The data were collected by means of an online questionnaire completed by community pharmacists across South Africa. The data were analyzed using descriptive statistics, through Microsoft Excel and the Statistical Package for the Social Sciences (SPSS). Results: Out of 250 online questionnaires sent, a total of 181 responded, which delivered an 72.4% response rate. The vast majority (n=166; 91.7%) of the respondents were knowledgeable about PC though a few (n=15; 8.3%) of the respondents had a poor understanding of PC. A high number of respondents (n=173;95.5%) agreed that providing PC would increase the patients’ confidence in the pharmacy profession (n=173; 95.5%); and about 87.2% responded that all pharmacists should provide PC services. Lack of compensation for PC provision was perceived as the main barrier (83.9%). Conclusion: South African community pharmacists have good knowledge of PC, but a lack of remuneration and time were perceived as the main barriers to PC provision. Relevant stake holders like policymakers in pharmaceutical service, health care financial managers, and pharmacy managers should intervene to overcome these barriers.