In England, the proportion of 13–15 year-olds who have ever drunk alcohol fell from 71% in 1999 to 35% in 2019. Despite substantial research literature studying this decline, we know little about connections with concurrent shifts in wider aspects of health and wellbeing. This paper aims to identify how indicators of health and wellbeing cluster within 15-year-olds in England, identify changes in clustering over time, and explore associations with sex and family affluence. We used latent class analysis of cross-sectional data from the Health Behaviours in School-aged Children study (n = 5,942; four waves 2001/02–2013/14). Classes were defined by indicators of substance use, sexual activity, diet, exercise, school-related measures, e-media use, parental relationships, and wellbeing. We identified three classes, which we labelled Overall unhealthy, Substance abstainers with behavioural risk indicators, and Overall healthy. The probability of being in the Overall unhealthy class fell (2001/02: 0.39; 2013/14: 0.18) while the probability of being in the Overall healthy class increased (0.21 to 0.41). The probability of weekly alcohol use fell in all classes (e.g. Overall unhealthy: 0.71 to 0.28). Females (female vs male OR: 1.74 95%CI: 1.30 – 2.34) and those with low family affluence (high vs low family affluence OR: 0.18 95%CI: 0.08 – 0.44) had significantly higher odds of being in the Overall unhealthy class. Overall, adolescents became more likely to have co-occurring indicators of good health and wellbeing, including reduced alcohol consumption, sexual activity and cigarette smoking. However, girls and those from poorer families remained more likely to have poor health and wellbeing.