Background: Antibiotic resistance is a threatening issue to human wellbeing and an obstacle in the treatment process of many life-threating illnesses. This study aims to assess the knowledge and attitudes toward antibiotic usage among the general population in Jeddah, Saudi Arabia. Methods: A self-administered cross-sectional survey of 460 participants was distributed among the general population in Jeddah in the form of a validated questionnaire. Sample size was calculated to be 460 adults of either gender. Descriptive and inferential statistical analyses were performed using the Statistical Package for Social Sciences. Results: the age of more than half of participants (55.6%) was 18–30 years old, followed by the age group 31–40 years old (26.6%), with the smallest age group >60 years old (1.9%). More than two thirds of participants were male (69.5%), while 131 were female, accounting for 30.5%. Almost one third of participants had poor knowledge about antibiotics (30.5%), 51.0% had used antibiotics without any prescriptions, 54.6% of participants thought antibiotics could be used to treat viral infections, and 55.1% thought it was acceptable to stop taking antibiotics if symptoms start to improve. In addition, 49% believed that taking antibiotics would help them get better more rapidly when suffering from the common cold. Some personal characteristics were significantly associated with the public’s knowledge (e.g., age, education, and monthly income) and their attitudes (e.g., monthly income). Conclusion: Findings revealed a low level of knowledge on the use of antibiotics among the general public in Jeddah. This study signifies the need for improvement in the public’s knowledge and enhancement of their attitudes toward proper utilization of antibiotics.