Background Many applications for registration of medicines are rejected because applicants fail to submit or resolve critical deficiencies in the quality, efficacy, and safety of the medicines. The study aimed to establish approval rates, processing timelines, and common deficiencies of generic medicines applications processed by the Medicines Authority of Zimbabwe (MCAZ). Method A retrospective study of applications finalized by MCAZ between 2018 and 2020 was conducted. Data were collected from the assessment reports and verified with copies of letters sent to the applicants. Deficiencies were classified as administrative, quality, efficacy, and safety. Other characteristics collated included time to finalization, dosage form, region of origin, and therapeutic class. Results Of the 579 finalized applications, 74.1% were approved while 25.9% were refused. Approved applications had more review cycles (median = 3 cycles) compared to refused applications (median = 2 cycles). However, refused applications had longer review times (median = 25 months) compared to approved applications (median = 18 months). The majority of applications (83.0%) were from Asian manufacturers and intended for oral administration (66.1%). Medicines for the endocrine system (50.0%) and rheumatism/gout (53.3%) had lower approval rates compared to other therapeutical classes (p < 0.001). The most common reasons for refusal of applications included failure to respond to review queries (52.6%), deficiencies in the API information (54.7%), FPP specifications (42.7%), FPP stability data (36.0%), and pharmaceutical development (31.3%). Conclusion To improve the quality of applications and evaluation outcomes, there may be a need for the regulatory authority to engage applicants through training and pre-submission meetings.