Background Coronavirus disease 2019 (COVID-19) has emerged as an important cause of morbidity and mortality worldwide. The aim of this study is to identify the clinical predictors of mortality among patients with COVID-19 pneumonia during first and second waves in a treatment center in northwestern Nigeria. Methods This was a retrospective cohort study of 195 patients hospitalized with COVID-19 between April 2020 to March 2021 at a designated COVID-19 isolation center in Kano State, Northwest Nigeria. Data were summarized using frequencies and percentages. Unadjusted odds ratios and 95% confidence intervals and p-values were obtained. To determine independent determinants of mortality, we performed a stepwise multivariate logistic regression model. Results Of 195 patients studied, 21(10.77%) patients died. Males comprised 158 (81.03%) of the study population. In the adjusted stepwise logistic regression analysis, age>64 years (OR = 9.476, 95% CI: 2.181–41.165), second wave of the pandemic (OR = 49.340, 95% CI:6.222–391.247), cardiac complications (OR = 24.984, 95% CI: 3.618–172.508), hypertension (OR = 5.831, 95% CI:1.413–24.065) and lowest systolic blood pressure while on admission greater than or equal to 90mmHg were independent predictors of mortality (OR = 0.111, 95%CI: 0.021–0.581). Conclusion Strategies targeted to prioritize needed care to patients with identified factors that predict mortality might improve patient outcome.