Purpose: This paper reports on a research study examining opportunities for and characteristics of effective leadership for whole university approaches to health, well-being and sustainability. Design/methodology/approach: A multi-method qualitative approach was used: semi-structured interviews and focus groups were conducted with vice chancellors (n = 12) and UK Healthy Universities Network members (n = 10) and online questionnaires were completed by non-UK network coordinators (n = 6) and non-UK health promoting university coordinators (n = 10), supplemented with two interviews. Findings: A total of two overarching themes emerged: opportunities to secure and sustain effective senior-level leadership and characteristics of effective senior-level leadership. Sub-themes under "Opportunities" included aligning work with core business so that health and well-being becomes a strategic priority, harnessing the personal qualities and values of senior-level advocates and using charters and policy drivers as levers to engage and catalyse action. Sub-themes under "Characteristics" included commitment to whole university/whole system working; an understanding that health underpins core business and is a strategic priority; enabling effective coordination through appropriate resourcing; balancing top-down and distributed leadership models and complementing strategic leadership with cultural change. Originality/value: This study is one of the first to explore leadership in relation to health promoting universities. Drawing on the findings, it presents a guide to developing and securing effective leadership for health promoting universities -- of value to researchers, practitioners and policymakers worldwide.