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Background Founded in 1925 as a ‘reverse Rhodes Scholarship’, the Harkness Fellowship was designed to foster international collaboration through transatlantic academic exchange. Over a century, it has evolved into a leadership programme uniting mid-career professionals from nine countries and a range of professional backgrounds to improve health systems through a year of immersion in the USA. As the fellowship marks its centennial, we reflect on what its history reveals about leading and learning across borders.Methods This centennial reflection draws upon archival research, programme documentation, alumni interviews and individual case studies. The analysis synthesises historical shifts, strategic pivots and leadership development outcomes over the programme’s 100-year history.Results Three core lessons emerged: (1) challenge assumptions—fellows consistently innovated by questioning entrenched practices and applying cross-cultural insights; (2) harness the power of fellowship—sustained relationships and a shared mission drive collaborative outcomes across borders and (3) embrace a multidisciplinary mindset—fellows from diverse fields have advanced more holistic approaches to healthcare reform. Real-world examples illustrate the fellowship’s tangible impact and provide practical lessons for healthcare leaders across countries and sectors.Conclusions The Harkness Fellowship demonstrates that leadership in healthcare demands curiosity, humility and sustained collaboration. The fellowship’s story is a reminder that the ability to learn across differences remains one of the most powerful tools for change. As the programme enters its second century, its relevance will rest on staying true to its core values: shared purpose, openness to difference and collaboration across borders to drive systemic change.