Laurie Benson and Catherine Quinn will leave the board when their terms come to an end in November, the commission said.
Benson has served on the board since November 2016 and is the chief executive of the media consultancy firm Upnexxt. Quinn was also appointed in November 2016 and is the private secretary to the Duchess of Cambridge.
The replacement board members will be paid £350 a day for 18 to 24 days’ work a year, depending on committee membership, the advertisement said.
Applications close on 19 June at 10am, with interviews to be held on 2 and 4 September.
The make-up of the Charity Commission board has provoked controversy in recent years, with the House of Lords Select Committee on Charities recommending the regulator "actively seek to recruit people from a wide range of demographic characteristics" to improve the board’s diversity.
The vacancies have also been highlighted on the website Conservative Home as part of a push by the website to increase the proportion of appointees to public offices that are Conservative party supporters.
Baroness Stowell, chair of the Charity Commission, said: "I would like to thank Laurie and Catherine for the tireless efforts and significant contributions they have both made during their time at the commission.
"They will leave the commission in a stronger position. I am very grateful to them for that and for being such great board colleagues."
Stowell said the new board members would arrive at a time when the commission was implementing a new five-year strategy "to fulfil our purpose of ensuring charity can thrive and inspire trust so that as much charitable benefit as possible is delivered to society".