Background Early diagnosis and adequate treatment of Group A streptococcal throat infection is an important initial stage in the primary prevention of acute rheumatic fever and rheumatic heart disease. This preventable condition associated with high mortality rates mandates a thorough understanding by the general public and the health. Objective The aim of the study was to assess the level of awareness about different aspects of rheumatic heart disease in patients coming to the outpatient department of the Buea regional Hospital, South West region of Cameroon. Methods This was a cross-sectional descriptive study carried in the outpatient department of the Buea Regional Hospital, Cameroon. The study population was adults and children aged 9 years and above. Data collection was done by using a self-administered questionnaire addressed to assess awareness on rheumatic heart disease. Results A total of 256 participants were interviewed, of which 70 (27.3%) were males. Their mean age was 34.4 ± 11.9 years (males: 36.2 ± 12.7 years versus females: 33.7 ± 11.6 years, p = 0.129). Most of the participants were in the 20 to 29 year old group (37.9%). More than two thirds (71.1%) of the participants reported having had sore throat at least once. The disease was treated with antibiotics in only 45.4%, with the treatment prescribed by a health care professional in 35.8% of the cases. About 73% of the respondents did not know what causes sore throat, and most (71.1%) were unaware of any complications that could arise from poorly treated sore throat. More than 70% of the participants did not know that sore throat can be associated with heart disease. Rheumatic heart disease was unknown to 82% of the participants and 95% of them did not know what causes RHD. Only 5.1% percent of the participants had an adequate knowledge of RHD. Age ≤ 35 years, post-secondary level of education, and having heard of RHD were significantly associated with an adequate knowledge. After adjusting for age, post-secondary education (aOR: 9, [95% C: 1.2±67.5], p = 0.019), and having heard of RHD (aOR: 18.1, [95% CI: 4.7±70.3], p<0.001) were still associated with a fair knowledge. Conclusions Levels of knowledge and awareness on rheumatic heart disease is low. This study provides important insight into the perception and practices related to sore throat that can be used in the design of awareness activities aimed reducing the risk of RHD in Cameroon. The appropriateness of antibiotics prescribed, and the health care provider awareness and knowledge levels regarding RHD in Cameroon has not been reported yet in the literature. This grey area deserves more research.