Objective: This study investigates the prevalence and determinants of self-medication practices among, the male and female, adult population in Karachi, Pakistan. Methods: This cross-sectional survey was conducted among 685 individuals from the general population through a structured questionnaire. The questionnaire covered demographics, questions related to self-medication, and attitudes towards utilization of self-medication and adherence to its safe practices. All individuals who were at least 18 years old and had been living in Karachi for a minimum of one year were included. The selection of households was done using a cluster sampling method, and only one individual was chosen to participate in the study. All healthcare professionals (doctors, nurses, pharmacists etc.) were excluded. Data was analysed using SPSS software version 22. Frequency tabulation and association between variables were seen using the Chi-square test. Logistic regression was applied to assess the independent associations of self-medication variables. All ethical issues were taken into consideration. Results: The prevalence of self-medication was found to be 43.6%. The most common symptoms for self-medication were fever 185 (61.9%), cough 159 (53.2%), and headache 120 (51.5%). The most commonly used drugs for self-medication were painkillers 147 (49.2%), cough syrups 131 (43.8%), and antibiotics 114 (38.1%). Notably, 80% of participants believed that certain medicines, such as antibiotics, should only be sold on a doctor's prescription. However, only 10% of participants thought that self-medication is a safe practice in Pakistan. The logistic regression analysis did not established any significant relationships between demographic characteristics and self-medication. Conclusion: This study found a high prevalence of self-medication in Karachi, Pakistan, with potential risks, especially for non-life-threatening conditions. It calls for increased awareness, education, and responsible implementation of self-medication practices. Healthcare professionals and policymakers should prioritize public awareness, healthcare education, and the involvement of healthcare professionals to promote accountable self-medication.