Background: This study aimed to compare demographics and cancer-specific variables in oncology patients hospitalized with (n = 551) and without COVID-19 (n = 3674) during the first year of the pandemic. Methods: We analyzed prospectively collected data from March 2020 to February 2021 at a major US cancer center, comparing age, sex, cancer category, race, metastasis, treatments within one month prior to admission, and smoking history. Results: The study found no significant difference in mean age between COVID and non-COVID cohorts (60.7% vs. 60.9%; p = 0.830). Significant differences (p = 0.002) in cancer categories were noted between COVID and non-COVID cohorts. Hematological cancers had the highest hospitalization rates in both groups (38.8% vs 29.2%). Statistically significant racial differences were observed between COVID and non-COVID cohorts (p < 0.001). Whites had the highest hospitalization rates in both groups, yet COVID-related admissions were lower for Whites (COVID cohort: 51.2% vs non-COVID cohort: 61.9%) and Asians (COVID cohort: 2.7% vs non-COVID cohort: 5.9%) compared to non-COVID admissions, while higher for Blacks (COVID cohort: 15.4% vs non-COVID cohort: 14%) and Hispanics (COVID cohort: 28.3% vs non-COVID cohort: 15.7). Significant differences (p < 0.001) were noted in metastasis prevalence between COVID and non-COVID hospitalizations, with rates of 81.3% and 86.0%, respectively. Conversely, non-metastatic cancer was more prevalent in COVID hospitalizations (18.1%) than in the non-COVID cohort (8.7%). In the COVID cohort, 30.5% received chemotherapy within one month before admission, compared to 43.8% in the non-COVID cohort, showing a significant difference in admission rates (p < 0.001). Similarly, recent immunotherapy (8.0% vs. 10.9%) and recent surgery (3.6% vs. 6.6%) were associated with higher hospitalization rates in the non-COVID cohort (p = 0.046 and p = 0.010, respectively). We observed significant differences (p < 0.001) in the smoking history of the COVID and. non-COVID cohorts. While 2.5% of COVID patients were current smokers, 5.4% of non-COVID patients were, more than double the COVID rate. In the COVID cohort, 36.3% were former smokers, slightly lower than the 37.6% in the non-COVID cohort. Additionally, 59.3% of COVID patients were never smokers, compared to 56.3% in the non-COVID group. Conclusions: COVID-related admissions were lower for Whites and Asians compared to non-COVID admissions, while higher for Blacks and Hispanics. Lower rates of metastasis were noted in COVID cohort. Lower rates of hospitalizations among patients who received chemotherapy, immunotherapy, and surgery were observed in the COVID cohort. The smoking prevalence was higher in the non-COVID group, former smoking rates were similar across cohorts, and a higher proportion of COVID patients were never smokers.