Prime Minister Shinzo Abe and foreign delegates will be among those observing a moment of silence at 8:15 AM local time (2315 GMT), when the detonation turned the western Japanese city into an inferno.
An American B-29 bomber named Enola Gay dropped an atomic bomb, dubbed "Little Boy", on Hiroshima on August 6, 1945, in one of the final chapters of World War II.
Nearly everything around it was incinerated, with the ground level hit by a wall of heat up to 4,000 degrees Celsius -- hot enough to melt steel.
On August 9, the port city of Nagasaki was also attacked with an atomic bomb, killing more than 70,000 people.
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Japan surrendered days later -- on August 15, 1945 -- bringing the war to a close.
Under-secretary for arms control Rose Gottemoeller will be the most-senior US official sent from Washington to the annual memorial.
US ambassador to Japan Caroline Kennedy will also be present at Peace Memorial Park in downtown Hiroshima.
Opinion remains divided over whether the twin attacks were justified.
Dropping the bombs, which were developed under strict secrecy, was hugely popular with war-weary Americans at the time -- and 70 years on, a majority today still think it was the right thing to do.
Fifty-six per cent of Americans surveyed by the Pew Research Centre in February said using the atomic bomb on Japanese cities was justified, compared to 79 per cent of Japanese respondents who said it was not.
Washington, which has been a close ally of Tokyo since the war, has never officially apologised for the bombings.