Background: There is limited evidence describing associations between cancer and function in diverse cancer types and its relationship with mortality. We investigated the relationship between cancer and poor ambulatory function and associations between ambulatory function and subsequent mortality. Methods: Participants included 233,135 adults (n = 30,403 cancer and n = 202,732 cancer free) in the NIH-American Association of Retired Persons Diet and Health Study (1994- 1996) who self-reported ambulatory function (e.g., walking pace and mobility disability: being unable to walk or walking at the slowest pace) in 2004-2006. Participants were followed for mortality from the assessment of ambulatory function through 2011. Multinomial logistic regression quantified the association between cancer and ambulatory function. We then explored the independent effects of walking pace and mobility disability in cancer survivors, and the joint effects of both a cancer diagnosis and poor ambulatory function on mortality using Cox proportional hazards models. Models explored type-specific associations across 15 cancer types. Results: Survivors had 42% greater odds of walking at the slowest pace [OR, 1.42 (confidence interval (CI), 1.30-1.54)] and 24% greater odds of mobility disability [OR, 1.24 (CI, 1.17-1.31)], compared with cancer-free participants, adjusting for baseline demographics, health indicators, and cancer type. Survivors reporting the slowest pace were at increased hazards than those who walked the fastest: all-cause mortality [HR, 2.22 (CI, 2.06-2.39)] and cancer mortality [HR, 2.12 (CI, 1.83-2.45)]. Similar trends emerged for mobility disability (HRs > 1.64). All-cause mortality associations were significant for more than nine cancer types. Conclusions: A diagnosis of cancer is associated with poorer ambulatory function, which is subsequently associated with increased mortality. Impact: Widespread efforts should target ambulatory function during cancer survivorship for survival benefits.