They commented as Hiroshima remembered its atomic bombing 79 years ago at the end of World War II.
The memorial comes days after Japan and the US reaffirmed Washington's commitment to "extended deterrence", which includes atomic weapons, to protect its Asian ally.
That is a shift from Japan's past reluctance to openly discuss the sensitive issue as the world's only country to have suffered atomic attacks.
Hiroshima Governor Hidehiko Yuzaki said nuclear-armed nations and supporters of atomic deterrence "deliberately ignore ... the fact that once people invented a weapon, they used it without exception".
Japan's Prime Minister Fumio Kishida laid a wreath at the Peace Memorial Park in Hiroshima,. (AP PHOTO)
"As long as nuclear weapons exist, they will surely be used again someday," Yuzaki said in his address at the Hiroshima Peace Memorial Park on Tuesday.
"Nuclear weapons abolition is not an ideal to achieve far in the future. Instead, it is a pressing and real issue that we should desperately engage in at this moment since nuclear problems involve an imminent risk to human survival," he said.
Hiroshima Mayor Kazumi Matsui said Russia's war on Ukraine and the worsening conflict between Israel and Palestinians are "deepening distrust and fear among nations" and reinforcing a view that use of force in settling conflict is unavoidable.
The atomic bomb dropped by the United States on Hiroshima on August 6, 1945, destroyed the city, killing 140,000 people. A second bomb dropped three days later on Nagasaki killed 70,000 more.
Japan surrendered on August 15, ending World War II and Japan's nearly half-century aggression in Asia.
About 50,000 people at the ceremony observed a minute of silence with the sound of a peace bell at 8:15am, the time when a US B-29 dropped the bomb. Hundreds of white doves were released.
Prime Minister Fumio Kishida, who attended the ceremony, said global conflicts and divided views over approaches to nuclear disarmament make achieving that goal "all the more challenging" but pledged to do his utmost in pursuing "realistic and practical measures" to build momentum within the international community.
His critics say it is a hollow promise because Japan relies on the US nuclear umbrella for protection.
