Objectives: Main objective was to systematically determine most frequently used medications among COVID-19 patients overall and by hospitalization status. Secondary objective was to measure use patterns of medications considered potential therapeutic options Design: Retrospective cohort study. Setting: The five academic medical centers of University of California Health. Participants: University of California COVID Research Data Set (UC CORDS) patients between March 10, 2020 and December 31, 2020. Exposure(s): Confirmed COVID-19 positive by SARS-CoV-2 nucleic acid amplification. Main Outcome(s) and Measure(s): Main outcomes were percentages of patients prescribed medications, overall, by age group, and by comorbidity based on hospitalization status. Use percentage by month of COVID-19 diagnosis was measured. Cumulative count of potential therapeutic options was measured over time. Results: Dataset included 22897 unique patients with COVID-19 (mean [SD] age, 42.4 [20.4] years; 12154 [53%] female). Among the sample, 6326 28%) were non-Hispanic White, 8475 (37%) were Hispanic, 1562 (7%) Asian, and 1313 (6%) Black. A COVID-related hospitalization occurred in 3546 patients. Of the hospitalized patients, more than 30% had baseline comorbidities of hypertension (48%), hyperlipidemia (37%), and type 2 diabetes (35%). Most frequently used medications in patients overall were acetaminophen (21.2%), albuterol (14.9%), ondansetron (13.9%), and enoxaparin (10.8%). Medications used were generally similar across ages and comorbidities. Prior to May, dexamethasone was rarely used, with well under 50 COVID-19 patients that had been hospitalized to that point receiving the medication. By mid-August, more than 500 patients to that point had received dexamethasone. Hydroxychloroquine use effectively halted in COVID-19 hospitalized patients after May. Throughout the period of March to December 2020, enoxaparin was used in the most patients to that point at any instance. By mid-December, more than 2000 in the analysis cohort of hospitalized patients had received enoxaparin. Conclusions and Relevance: In this retrospective cohort study, across age and comorbidity groups, predominant utilization was for supportive care therapy. Dexamethasone and remdesivir experienced large increases in use. Conversely, hydroxychloroquine and azithromycin use markedly dropped. Medication utilization rapidly shifted towards more evidence-concordant treatment of patients with COVID-19 as rigorous study findings emerged.