Thompson said that his speech is well timed as the finely balanced outcome of 2010's general election heralds "a big year for the BBC". The corporation is facing major change to its operation, including Thompson's controversial strategy review currently being under public consultation at the BBC Trust.
However, Thompson will also have to follow last year's lecture from News Corporation Asia and Europe boss James Murdoch, who used the platform to criticise the BBC.
In his speech, Murdoch claimed that the corporation is unable "to distinguish what is good for it, and what is good for the country", and also called for the BBC to be reduced in scale.
Speaking about his MacTaggart speech on August 27, Thompson said: "In what is a big year for the BBC as well as the rest of the broadcasting industry, it's a great privilege to be asked to give the MacTaggart lecture, and I'm looking forward to it."
The festival's advisory chair Deborah Turness, who is also editor of ITV News, added: "Edinburgh is the first stop on the media calendar following the general election, and the MacTaggart will once again set the agenda for the weekend.
"In what promises to be a pivotal year for the BBC, I am delighted that Mark has agreed to share his vision with the Edinburgh audience."
The MacTaggart lecture is often a platform for controversial speeches delivered by high-profile industry figures, with previous speakers including Dennis Potter, Ted Turner, Jeremy Paxman and Rupert Murdoch.
Thompson joins former BBC director general Jon Birt as the only television executives to deliver two MacTaggart speeches. His previous lecture was in 2002 as chief executive of Channel 4, when he took the opportunity to criticise the "dull, mechanical and samey" nature of British television.