Background: The COVID-19 pandemic posed numerous challenges to public health systems, particularly in antimicrobial stewardship. This study aimed to assess antibiotic consumption before and during the COVID-19 pandemic to evaluate the effectiveness of the implemented antimicrobial stewardship program. Methods: This retrospective study was carried out at the University Hospital in Krakow, Poland, between 1 January 2019 and 31 December 2020. A total of 80,639 patients were enrolled. Antibiotic usage was measured as the percentage of patients receiving antibiotics and the number of days of therapy (DOTs). The World Health Organization (WHO) methodology and Anatomical Therapeutic Chemical (ATC) codes and AWaRe classification were utilized. The analyzed ATC antibiotic groups included penicillins (J01CA, J01CE, J01CF, J01CR, excluding piperacillin/tazobactam), piperacillin with tazobactam-beta-lactamase inhibitor (J01CR05), third- and fourth-generation cephalosporins (J01DD, J01DE), carbapenems (J01DH), macrolides (J01FA), fluoroquinolones (J01M), colistin (J01XB01), metronidazole (J01XD01) and others (J01DF, J01DI, J01E, J01G, J01XA, J01A). In the AWaRe classification, Access, Watch and Reserve groups of antibiotics were included. Results: In 2020, 79.2% of COVID-19 patients and 40.1% of non-COVID-19 patients were treated with antibiotics, compared to 28.8% in 2019. Also, in 2020, the antibiotic consumption in non-ICU COVID-19 patients was twice as high as in non-COVID-19 patients: 50.9 vs. 38.5 DOTs/100 patient days (pds). Conversely, in the ICU, antibiotic consumption in COVID-19 patients was 112.1 DOTs/100 pds compared to 248.9 DOTs/100 pds in non-COVID-19 patients. Significant increases were observed in the usage of third- and fourth-generation cephalosporins in 2020. The analysis according to the AWaRe system revealed the highest usage of the Watch group—ranging from 61.9% to 78.7%—and very high usage of the Reserve group—from 5.8% to 11.1%—in non COVID-19 and COVID-19 patients, respectively. Conclusions: Our findings highlight substantial issues with antibiotic use both before and during the COVID-19 pandemic. The results underscore the urgent need for improved antimicrobial stewardship policy implementation.