Amphetamine-type stimulants (ATS) are the second most commonly used class of illicit drugs globally, yet there is limited understanding of which factors contribute to different pathways of ATS use. We sought to compare current, former, and exposed non-ATS users’ substance use, mental/physical health, and adverse life experiences. A cross-sectional survey, using computer-assisted personal interview software, was conducted between June 2018 and March 2019 in North East England. Quota-based sampling was used to recruit 389 individuals (aged 18 to 68; 52.6% male): 137 current ATS users; 174 former users; and 78 exposed non-users. Standardized screening questionnaires captured current/prior substance use. Participants self-reported diagnoses of selected physical and mental health disorders and specific adverse life experiences. Analysis used descriptive statistics and comparative tests (including chi-square, Kruskal–Wallis and Mann–Whitney U). Early exposure to illicit substances, challenging mental health, and certain adverse life experiences (such as growing up in statutory care) were more common in individuals currently using ATS compared to those who had never used or stopped using stimulants. Multi-level interventions are needed that address the mental health, social, and economic needs of people with dependent drug use. These could include targeted efforts to support children growing up under care, integrated mental health and substance use support, and joined-up substance use interventions reflective of wider structural factors.