Purpose: Ultra-processed foods make up more than 50% of daily energy consumed in Western countries and are rapidly increasing in China. However, little is known about the association between ultra-processed food intake and muscle strength, a predictor for physical disability in senior years. We aimed to investigate the association of ultra-processed food intake with longitudinal changes in grip strength among middle-aged and older Chinese adults. Methods: This prospective cohort study included a total of 5409 adults aged 40 years and over (61.3% men). Ultra-processed food intake was obtained by means of a validated food frequency questionnaire and classified according to the NOVA classification system. Grip strength was measured annually using a handheld digital dynamometer. Multivariable linear regression models were used to examine the association between ultra-processed food intake and annualized change in grip strength and weight-adjusted grip strength. Results: In the fully adjusted models, annualized changes in grip strength and weight-adjusted grip strength per 10% increment in the proportion of ultra-processed foods in the diet were − 0.3708 kg (95% confidence interval − 0.5687, − 0.1730; P < 0.001) and − 0.0057 kg/kg (95% confidence interval − 0.0086, − 0.0029; P < 0.0001), respectively. In analyses stratified by age, sex, body mass index, physical activity, hypertension, hyperlipidemia, diabetes, and healthy diet score, such associations were largely consistent in most subgroups (all P for interaction > 0.05). Conclusions: Our data indicate that higher ultra-processed food intake was associated with faster grip strength decline in middle-aged and older Chinese adults.