The rational use of drugs in veterinary medicine has various significances, such as reducing the risk of drug resistance, increasing efficacy, reducing drug residue, and decreasing adverse drug reactions. A retrospective study was conducted to assess veterinary drug prescribing practices at Batu and Arsi-Negelle district veterinary clinics in the rift valley areas of Ethiopia. A total of 2,464 cases were recorded from the case registration books at both the clinics for diseases treated between September 2012 and February 2015. The study results showed that for a total of 2,464 cases diagnosed at both clinics, 3,811 different drugs were prescribed, with an average per encounter of 1.6. Among the total drugs, oxytetracycline, ivermectin, penstrep, sulfa drugs, and albendazole were the most leading prescribed drugs with a frequency of 43.0%, 17.6%, 10.2%, 6.5%, and 1.3%, respectively. All drugs were prescribed by the generic name without any laboratory support of the disease. About 68.3% of the cases were diagnosed by unspecified professionals, whereas 21.7% and 10.1% were done by animal health assistants and veterinarians, respectively. The prescribing practices showed 61.0% of antibiotics and 29.7% of anthelmintics where 45.3% and 54.7% of antibiotics and 17.8% and 82.2% of anthelmintics were given at Batu and Arsi-Negelle veterinary clinics, respectively. Of the prescribed drugs, 4.6% oxytetracycline and 2.6% penstrep were prescribed irrationally to treat diseases that were tentatively diagnosed as parasitic cases. Similarly, 40.5% ivermectin and 17.7% albendazole were prescribed for bacterial infections. In conclusion, this study revealed problems in antibiotics and anthelmintics use, description of routes of administration and length of treatment, and shortage of laboratory diagnostic facilities. Therefore, veterinary drugs, particularly antibiotics and anthelmintics, should be used appropriately to safeguard the public from residual drug impacts and resistance development.