UPDATE: Henderson's resignation was formally confirmed by the agency the day after this story was published. Click here to read his statement
It comes ahead of the announcement of what action will be taken after Bell Pottinger was ruled to have breached the PRCA’s code of conduct.
Bell Pottinger's allegedly racially divisive work with Oakbay, which is owned by allies of South Africa's president Jacob Zuma, was the subject of a complaint by the opposition party Democratic Alliance, at a hearing on 18 August.
It has since been confirmed that the PRCA's professional practices committee concluded that the agency was in breach of its code, although Bell Pottinger has appealed that decision.
Bell Pottinger has previously admitted that its work for Oakbay was "inappropriate and offensive" and fired the partner it held responsible.
Bell Pottinger has yet to release a statement on Henderson’s resignation, although he told the BBC on Sunday: "Whilst I had no involvement in the account, there were warning signs that I should have heeded. Therefore I must take responsibility."
An official statement by the company will be published on Monday (4 September), as well the external law firm's report into the company.
The resignation of Henderson, whose stake in Bell Pottinger stands at more than 20 per cent, adds further uncertainty to the future of the agency.
Henderson admitted last month that "a number" of clients had left the firm since the allegations around Bell Pottinger’s activities in South Africa came to light. Bell Pottinger said in April that it had stopped working with Oakbay.
It is rumoured that chairman Mark Smith has been made acting CEO with immediate effect, but that Hugh Taggart will be made interim CEO in due course. The business was not able to immediately confirm this.
Lord Bell, co-founder of the business and its chair until August last year, said of Henderson's resignation: "I think it's an empty gesture... it’s called 'I'm taking my bat and going home', it doesn’t solve anything, it just leaves a mess."
Asked whether the case would have wider impacts for the PR industry, he said: "No I don't think so, it's just some local difficulty, it doesn't affect the whole industry."
Sam Burne James also contributed to this report, which was updated with additional comment and details on 4 September