The health of an individual is determined by the interaction of genetic and individual factors with wider social and environmental elements. Public health approaches to improving the health of disadvantaged populations will be most effective if they optimise influences at each of these levels, particularly in the early part of the life course. In order to better ascertain the relative contribution of these multi-level determinants there is a need for robust studies, longitudinal and prospective in nature, that examine individual, familial, social and environmental exposures. This paper describes the study background and methods, as it has been implemented in an Australian birth cohort study, Environments for Healthy Living (EFHL): The Griffith Study of Population Health. EFHL is a prospective, multi-level, multi-year longitudinal birth cohort study, designed to collect information from before birth through to adulthood across a spectrum of eco-epidemiological factors, including genetic material from cord-blood samples at birth, individual and familial factors, to spatial data on the living environment. EFHL commenced the pilot phase of recruitment in 2006 and open recruitment in 2007, with a target sample size of 4000 mother/infant dyads. Detailed information on each participant is obtained at birth, 12-months, 3-years, 5-years and subsequent three to five yearly intervals. The findings of this research will provide detailed evidence on the relative contribution of multi-level determinants of health, which can be used to inform social policy and intervention strategies that will facilitate healthy behaviours and choices across sub-populations.