Background Sleep duration, physical activity, and nutrition (SPAN) are each associated with mortality risk, yet they are usually examined individually or in pairs, with limited attention to their combined associations and differences across physical activity domains. We examined combined SPAN behaviours in relation to all-cause mortality across different physical activity domains (occupational physical activity (OPA), leisure-time physical activity (LTPA) and transportational physical activity (TPA)). Methods We included adults aged 18 years or older from the National Health and Nutrition Examination Survey 2007-2018. Sleep duration was self-reported in hours/day. Physical activity, including moderate-to-vigorous physical activity (MVPA) across domains, was assessed using the Global Physical Activity Questionnaire. Diet quality was estimated from 24-hour dietary recalls using the Healthy Eating Index-2020 (HEI-2020). We created 27 mutually exclusive joint categories using tertiles of physical activity and HEI-2020, and guideline-based sleep-duration groups (8 h/day), with the lowest combination as the reference. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs for all-cause mortality. To estimate the minimum combined variations associated with lower mortality risk, we used the 5th percentile of each behaviour as the reference. Results Among 31,875 participants (median age 48.0 years; 51.4% female), 2,623 deaths occurred over a median follow-up of 6.75 years. In joint categorical analyses, a combination of optimal sleep (7-8 h/day), high diet quality (HEI-2020: >56.0), and high LTPA (>35.4 min/day) or high TPA (>25.7 min/day) was associated with the lowest all-cause mortality risk (HR = 0.44, 95%CI: 0.29-0.65; HR = 0.54, 95%CI: 0.37-0.77). The lowest HR for OPA was observed for sleep duration (3.-6.5 h/day), moderate OPA (1.4-114.0 min/day), and high diet quality (HR = 0.53, 95%CI: 0.37-0.75). Relative to the reference values (sleep: 5 h/day, MVPA/PA domains: 0 min/day and HEI-2020: 32.29), a combined minimum increment of 15 min/day of sleep, 5 HEI-2020 points, in combination with either 10.8 min/day of total MVPA, 24.0 min/day of OPA, or 5.2 min/day of LTPA, were associated with 10% lower all-cause mortality. For TPA, the 10% lower risk corresponded to 30 additional min/day of sleep, 5 HEI-2020 points, and 5.5 min/day of transport PA. Conclusions Modest combined increments in SPAN were associated with lower all-cause mortality among US adults across physical activity domains, with combinations including higher amounts of LTPA showing the most favourable profile.