Objective To estimate the impact of the COVID-19 pandemic on cardiovascular disease (CVD) mortality trends in Mexico. Methods An ecological study was conducted where deaths from CVD reported in Mexico under the ICD-10 classification with codes I10 to I99 for the period 2000–2022 were analyzed. Age-standardized mortality rates were calculated at the national and state levels, then the annual percentage variation was estimated using joinpoint analysis to know the changes in the mortality trend in the period studied. Results There was an increase of 27.96 deaths per 100,000 inhabitants from 2000 to 2022 in Mexico. The joinpoint analysis shows in the period 2019–2021 an annual percentage change at the national level of 17,398 and subsequently a negative trend is presented between the years 2021–2022. The states of Guanajuato, Tlaxcala and Querétaro showed the largest increases in CVD mortality trends during the COVID-19 pandemic. Conclusions The trend in CVD mortality in Mexico increased significantly during the COVID-19 pandemic.