Background: Age-related decline in muscle strength, dynapenia, is linked to serious adverse health outcomes. Evidence on the determinants of muscle strength decline in the oldest old is lacking. Aims: To identify clinical variables associated with handgrip strength and its change over a 4-year period in an oldest old cohort. Methods: We included 555 participants from the Leiden 85-plus Study, a prospective population-based study of 85-year-old inhabitants of Leiden, the Netherlands. Handgrip strength was assessed at age 85 and 89 years. Anthropometry, mental status, functional performance, and biochemical variables were obtained at baselines. Significant univariates were included into multivariable regression models to extract the final predictive variables. Results: Handgrip strength for men and women at age 85 years was 30.6 kg (SD 8.2) and 18.7 kg (SD, 5.5), respectively. In the cross-sectional analysis, body height and weight were positively associated with handgrip strength in both genders. Higher functional performance was associated with stronger handgrip strength in women. Mean absolute handgrip strength decline over 4 years was greater for men than women (− 6.1 kg (SD, 5.2) vs. − 3.4 kg (SD, 4.1), p < 0.001). Men with better baseline cognitive functioning had smaller decline in handgrip strength. Conclusions: This study further strengthens evidence linking functional and cognitive performances to muscle strength in the oldest old. Future research is needed to ascertain causality and determine if these markers represent potential targets for intervention.