Warren Buffett is leaving the board of the Gates Foundation, casting further uncertainty over the world’s largest private philanthropic organisation after its co-chairs, Bill and Melinda Gates, announced they were divorcing.

Buffett, the legendary American investor and chair of Berkshire Hathaway, became a trustee of the foundation, alongside his friends the Gateses, after announcing in 2006 that he would donate the bulk of his fortune to charity.

“For years I have been a trustee — an inactive trustee at that — of only one recipient of my funds, the Bill & Melinda Gates Foundation (BMG). I am now resigning from that post, just as I have done at all corporate boards other than Berkshire’s,” Buffett said in a statement on Wednesday.

He also praised the foundation’s chief executive, Mark Suzman, as “outstanding” and said his goals remained “100 per cent in sync with those of the foundation”.

With a $50bn endowment, the Gates Foundation is not only the largest private philanthropy group, it is also regarded as the most influential. It has channelled the vast wealth Bill Gates amassed as co-founder of Microsoft into campaigns to eradicate diseases such as polio and reduce childhood mortality. Its long-term work on vaccines has made it a key player in the fight against coronavirus.

But its future has come into question after the Gateses announced in early May that they would be ending their 27-year marriage. In a statement issued at the time, they insisted they remained committed to the foundation’s mission and would “continue our work together at the foundation”.

Some former employees and advisers have questioned whether the institution the couple has dominated throughout its 21-year existence can continue in its current state in light of their split. Others are convinced that it has built sufficient institutional muscle over the years to thrive in any case. The Foundation staff now numbers more than 1,600.

In addition to the Gates Foundation, Bill and Melinda Gates each pursue their own separate philanthropic activities. In 2015, for example, Melinda launched an investment vehicle, Pivotal Ventures, which aims to support gender equality.

Suzman, who was appointed chief executive last year, confirmed earlier this month that the Gateses were considering the possibility of adding outside directors to the board as part of “prudent planning for the future”.

In a note to staff on Wednesday, he acknowledged the uncertainty stirred by Buffett’s resignation. “I know Warren’s departure raises questions about the foundation’s governance. As I have mentioned previously, I have been actively discussing with him, Bill, and Melinda approaches to strengthen our governance,” he wrote, promising further details in July.

Suzman also thanked Buffett for his latest contribution — a $3.2bn gift announced on Wednesday that will bring his total donations to the Foundation to nearly $33bn.

In the same note, Melinda said she was “grateful for Warren’s generosity, his leadership, and his friendship”, while Bill paid tribute to his “enduring friendship” and said the foundation “will always have a deep sense of accountability to Warren, paying close attention to the data to track our progress and identify areas where we can do better”.

Phil Buchanan, president of the Center for Effective Philanthropy, questioned the timing of Buffett’s announcement, so close to the expected unveiling of further governance changes, saying: “In an ideal world you’d be able to announce some new additions to the board at the same time as you announced a major departure but the world is not always ideal.”

Buchanan also reflected on the wider significance of any shifts at an institution that has become so dominant in philanthropy and public health.

“As the largest foundation in the world, the governance of the Gates Foundation matters both substantively in terms of sound decision-making and symbolically for what signal it sends about institutional philanthropy and its oversight and accountability,” he said.