Background: Consumers and caregivers should remove expired, or unwanted, medications to minimize the chance for misuse or accidentally using those medicines. This study investigated pharmacists’ knowledge regarding drug disposal in Karbala, Iraq. Methods: This study was a cross-sectional survey among pharmacists in Karbala. It was performed from December 2018 until January 2019. A standardized, 12-item, self-administered questionnaire was designed, developed and validated to assess pharmacists’ knowledge when generating pharmaceutical waste in pharmacies. Results: One hundred twenty-nine participants enrolled in the study. The mean age of participants was 33 ± 9.3 years—more than two-thirds (65.9%)—agreed that the return of medications to the source would be appropriate drug disposal. A good proportion of participants agreed with disposing of drugs in the trash. Further, 63.6% believe that education is the main barrier opposing the implementation of a medicine–take–back program in Iraq. Conclusion: Pharmacists had relatively poor knowledge regarding drug disposal methods. Health care providers (not only pharmacists) need educational courses and workshops to improve their knowledge regarding medication disposal in Iraq.