The relationships of physical activity and sedentary time with all-cause mortality in those at high risk of type 2 diabetes mellitus (T2DM) are unexplored. To address this gap in knowledge, we examined the associations of objectively measured moderate-to-vigorous-intensity physical activity (MVPA) and sedentary time with all-cause mortality in a population of adults at high risk of T2DM. In 2010–2011, 712 adults (Leicestershire, U.K.), identified as being at high risk of T2DM, consented to be followed up for mortality. MVPA and sedentary time were assessed by accelerometer; those with valid data (≥ 10 hours of wear-time/day with ≥ 4 days of data) were included. Cox proportional hazards regression models, adjusted for potential confounders, were used to investigate the independent associations of MVPA and sedentary time with all-cause mortality. 683 participants (250 females (36.6%)) were included and during a mean follow-up period of 5.7 years, 26 deaths were registered. Every 10% increase in MVPA time/day was associated with a 5% lower risk of all-cause mortality [Hazard Ratio (HR): 0.95 (95% Confidence Interval (95% CI): 0.91, 0.98); p = 0.004]; indicating that for the average adult in this cohort undertaking approximately 27.5 minutes of MVPA/day, this benefit would be associated with only 2.75 additional minutes of MVPA/day. Conversely, sedentary time showed no association with all-cause mortality [HR (every 10-minute increase in sedentary time/day): 0.99 (95% CI: 0.95, 1.03); p = 0.589]. These data support the importance of MVPA in adults at high risk of T2DM. The association between sedentary time and mortality in this population needs further investigation.