With the evolving coronavirus disease-2019 (COVID-19) pandemic, India witnessed multiple peaks with dissimilarities at various levels. We conducted a cross-sectional study on COVID-19 patients admitted at a tertiary care hospital in Himachal Pradesh, India, during the peak of the first wave (from 1 November 2020 to 20 November 2020), the second wave (from 20 April 2021 to 10 May 2021), and the third wave (from 15 January 2022 to 15 February 2022) to evaluate differences in the clinico-demographic profile and treatment outcomes. A total of 300 confirmed cases of COVID-19 were included in the analysis, 100 from each wave. The mean age (in years) of study participants during the first, second, and third waves was [mean ± standard deviation (SD)] 56.94 ± 14.80, 54.92 ± 14.98, and 61.29 ± 18.69, respectively; p = 0.16. Males outnumbered females in all three waves. The hospital stay was maximum during the second wave (mean ± SD; 12.22 ± 8.81 days) when compared to the first (5.21 ± 3.43 days) and third waves (3.71 ± 2.74 days); p = 0.008. Fever and cough were primarily reported in the first wave (with p < 0.001 and p = 0.001, respectively). Gastrointestinal symptoms were more common in the second and third waves (p < 0.001). Diabetes, hypertension, and cardiovascular diseases were common underlying diseases among admitted patients in three waves. Total leukocyte count, neutrophil-to-lymphocyte ratio, and erythrocyte sedimentation rate were higher in the second wave (p = 0.004; p < 0.001; and p < 0.001, respectively). The incidence of liver dysfunction was more common in the second wave. The second wave was deadly both in terms of severity and mortality as compared to the first and third waves. The younger age-group (18–40 years) was largely affected during the second wave while the elderly age-group was primarily affected during the third wave.