Introduction: Antihistamines are the most used drugs in the treatment of allergies. Approximately a dozen drugs are available on the pharmaceutical market, and their generic forms are marketed widely as very efficient drugs for the treatment of allergic diseases. Usually, people receive antihistamines as an inexpensive, generic, over-the-counter drug that can deliver relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with minimal side effects. Aim: The study aimed to assess public awareness regarding antihistamines and their prescription in PHCCs in Abha City, Saudi Arabia. Methodology: A descriptive cross-sectional approach was used targeting all accessible population in Abha city, Aseer region, Southern of Saudi Arabia. All those with ages of 18 years or more living in Abha region and attending primary health care centres were invited to participate in the survey. Data were collected from participants using electronic pre-structured questionnaire. The tool covered the following data: participants' socio-demographic data like age, gender, residence, education, participants' history for receiving antihistamines, and participants practice regarding antihistamines, role of physician and pharmacists within PHCCs in providing health education (HE) sessions for antihistamines, participants' satisfaction regarding medical staff role and provided HE. Results: The study included 800 participants whose ages ranged from 18 to 55 years with mean age of 27.5 +/- 10.9 years old. The majority of participants were females (73.5%; 588). As for known formulas of antihistamines, pills were the most reported formula (98.5%) followed by syrup (7.8%), nasal spray (3.8%), and eye drops (2.4%). Exactly 420 (52.5%) of the participants previously had antihistamines without prescription. The main cause of that was being available and easily achieved (82.6%). Conclusion: In conclusion, the study revealed that public awareness regarding antihistamines was very poor especially concerning their types and clinical effects. Also, unprescribed utilization of antihistamines was very high due to their availability and being easily achieved.