Abstract Background Although sarcopenia has been linked to a range of cardiometabolic diseases (CMDs, including coronary heart disease [CHD], stroke, and diabetes here), its role in the temporal progression from healthy to single CMD, subsequently to cardiometabolic multimorbidity (CMM, coexistence of ≥ 2 CMDs in an individual), and further to death remains unclear. In this study, we aimed to examine the associations of sarcopenia with the risk of CMDs, CMM, and mortality along the CMD progression trajectory. Methods We used data from UK Biobank of 413,326 participants free of CMDs at baseline. Multi-state models were used to analyze the transition-specific associations of sarcopenia status measured by handgrip strength, muscle mass, and gait speed (according to the 2019 European Working Group of Sarcopenia in Older People 2) with the progression from no CMD to single CMD, CMM, and ultimately to death. The role of specific sarcopenia components was also assessed. Results During a median follow-up of 13.1 years, 51,705 participants experienced ≥ 1 CMD, 6,003 had CMM, and 24,495 died. Compared with people free of sarcopenia, participants with confirmed/severe sarcopenia had higher risk experiencing transitions from no CMD to single CMD or death (hazard ratio [HR] 1.42 and 2.08) and also higher risk from single CMD to CMM progression or death (HR 1.69 and 2.05). Significant associations were observed for participants with probable sarcopenia with smaller effect sizes. All three sarcopenia components increased the risk of most transitions, and stronger associations were observed for low gait speed. In stratified analyses, the associations between sarcopenia and mortality-related transitions were modified by specific lifestyles. Conclusions Sarcopenia is an independent risk factor of CMD, CMM progression, and all-cause mortality among middle-aged and older people.