Background. Medicines have become part of our day-to-day life. Due to different reasons, patients may not use all the medications dispensed to them. The storage of drugs at home promotes self-medication, which results in variety of adverse consequences. Global growth in health-seeking awareness and behavior among people has resulted in increment of medicine consumption over years. However, Ethiopians have little awareness about proper disposal of unused and expired pharmaceuticals. Besides, large quantities remain unused or expired since not all medications given to the consumers are consumed. Hence, this study could serve as an indicator for the country policy makers concerning pharmaceutical waste management. Objective. To assess knowledge, attitude, and disposal practice of unused and expired pharmaceuticals in the community of Adigrat city, Tigray, Ethiopia, 2019. Methodology. A cross-sectional study was conducted among 359 respondents from the residents of Adigrat city. Semistructured questionnaires, which focused on knowledge, attitudes, and disposal practices for unused and expired medications, were used to collect data from respondents. Epi-data 3.0 suite and the statistical package for social sciences (SPSS) version 20 were used in data entry and analysis. Results. All of the 359 returned questionnaires were valid for data entry and analysis. Of the 359 respondents, 57.7% were men and the majority (93%) were Orthodox Christians. Almost half of the respondents (50.14%) have good knowledge concerning the disposal of unused and expired pharmaceuticals. Most (82.2%) of the respondents have a positive attitude towards the disposal of unused and expired pharmaceuticals. Around fifty-two (52.4) of the respondents had unused medicines stored at home, with analgesics being the most common (41.5%). Around three-quarters (75.2%) and 63% of the respondents discarded unused and expired medicines in the garbage bins, respectively. Conclusion. Although the majority of the respondents had a positive attitude towards the disposal of unused and expired medications, almost half of the sample population were unaware of proper disposal practices. Furthermore, less were inclined to practice proper disposal of unused and expired medications in the city. Therefore, we recommend further studies that focus on how the disposal attitude of the population can influence their knowledge and practice of the disposal of unused and expired medications.