The Royal Academy said the work will be part of an exhibition on Depression era art.
It shows an Iowa farmer holding a pitchfork with his daughter by his side and a house in the background.
America After the Fall: Painting in the 1930s opens on 25 February 2017 and will run until 4 June.
American Gothic was part of the American Regionalism movement which saw artists attempt to reflect the regions affected by the Great Depression, triggered by the Wall Street Crash of 1929.
Tim Marlow, director of artistic programmes at the Royal Academy, said it had "never left American soil" before and is "metaphorically embedded in the American soil in the Midwest".
"From the beginning, it has been seen as an icon because it's emblematic of American regionalism, a kind of quiet, understated power," he said.
Marlow said American Gothic was "slightly sidelined as a mere populist painting" but was now seen as "something that is both popular but also deeply profound".
The painting has a newfound "resonance" as the US gears up for the forthcoming presidential election, he said.
"I think it will be wonderful to see it decontextualised out of America and recontextualised in London," Marlow added.
The painting is one of 45 from the period that will be displayed.
Works by Thomas Hart Benton, Jackson Pollock, Edward Hopper and Georgia O'Keefe will also be included.
Other highlights among the Royal Academy's 2017 programme include an exhibition of the work of Jasper Johns.
The RA said the exhibition from 23 September to 10 December, which will include his paintings, sculptures, prints and drawings, would "give focus to different chapters of Johns' career".
Johns, who is 86 years old, is widely seen as one of the greatest living painters.
Another exhibition, Matisse in the Studio, will run between 5 August and 12 November and show how Henri Matisse's personal collection of treasured objects influenced his work.
Other exhibitions to be announced for next year include Revolution: Russian Art 1917 - 1932 and Dali/Duchamp, which will focus on the friendship and works of Marcel Duchamp and Salvador Dali.
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American Gothic, the iconic painting by Grant Wood, is coming to London next year - the first time it will have been seen outside of North America.