Background Sleep, physical activity, and nutrition (SPAN) are critical behaviours for health, although they have traditionally been studied separately. We examined the combined associations of SPAN and the minimum between-individual variations associated with meaningfully lower all-cause mortality risk. Methods This prospective cohort analysis included 59,078 participants from the UK Biobank (median age: 64.0 years; 45.4% male) who wore trackers for 7 days and self-reported dietary data. Wearable-measured sleep (hours/day) and moderate to vigorous physical activity (MVPA; mins/day) were calculated using a machine learning based schema. A 10-item diet quality score (DQS) assessed the intake of vegetables, fruits, fish, dairy, whole grains, vegetable oils, refined grains, processed and unprocessed meats, and sugary beverages (0–100 for all components with higher values indicating higher quality). Cox proportional hazards models were used to estimate hazard ratios (HR) for all-cause mortality risk across 27 separate joint tertile combinations of SPAN behaviours with the lowest tertile for all three as the referent group. For more granular clinical interpretations, we examined combined incremental dose–response changes of the SPAN behaviours using the 5th percentile of each behaviour as the referent point. Results Over the 8.1-year median follow-up time, 2,458 mortality events occurred. Compared to the referent group of combined SPAN exposure (lowest tertiles for all three), the optimal SPAN combination involving moderate sleep duration (7.2–8.0 h/day), high MVPA (42–103 min/day), and a DQS between 57.5 and 72.5 was associated with an HR of 0.36 (95% CI: 0.26–0.50). Relative to the 5th percentile of sleep (5.5 h/day), physical activity (7.3 min/day), and nutrition (36.9 DQS), a theoretical minimum combined increase of 15 min/day of sleep, 1.6 min/day MVPA, and 5 DQS points (corresponding to e.g., extra 1/2 serving of vegetables per day or 1 less serving of processed meat per week) was associated with 10% lower all-cause mortality risk (0.90; 0.88–0.93). Combined increases of 75 min/day of sleep, 12.5 min/day MVPA, and 25 DQS points were associated with 50% lower all-cause mortality risk (0.50; 0.44–0.58). Conclusions This study highlights the potential health value of subtle combined SPAN modification in relation to mortality risk and expands opportunities for more holistic recommendations.