Although it is widely used as a measure for mortality, the case fatality rate (CFR) ofcoronavirus disease 2019 (COVID-19) can vary over time and fluctuate for many reasons otherthan viral characteristics. To compare the CFRs of different countries in equal measure, weestimated comparable CFRs after adjusting for multiple covariates and examined the mainfactors that contributed to variability in the CFRs among 21 countries. For statistical analysis, time-series cross-sectional data were collected from OurWorld in Data, CoVariants.org, and GISAID. Biweekly CFRs of COVID-19 were estimated bypooled generalized linear squares regression models for the panel data. Covariates includedthe predominant virus variant, reproduction rate, vaccination, national economic status,hospital beds, diabetes prevalence, and population share of individuals older than age 65. Intotal, 21 countries were eligible for analysis. Adjustment for covariates reduced variation in the CFRs of COVID-19 across countriesand over time. Regression results showed that the dominant spread of the Omicron variant,reproduction rate, and vaccination were associated with lower country-level CFRs, whereasage, the extreme poverty rate, and diabetes prevalence were associated with higher countrylevel CFRs. A direct comparison of crude CFRs among countries may be fallacious, especiallyin a cross-sectional analysis. Our study presents an adjusted comparison of CFRs over timefor a more proper comparison. In addition, our findings suggest that comparing CFRs amongdifferent countries without considering their context, such as the epidemic phase, medicalcapacity, surveillance strategy, and socio-demographic traits, should be avoided.