Obama said that "71 years ago on a bright, cloudless morning, death fell from the sky and the world was changed."
"A flash of light and a wall of fire destroyed a city, and demonstrated that mankind possessed the means to destroy itself," the President added during his address at the site of the first nuclear bombing.
Obama was not expected to apologize for the U.S. action to hasten the end of World War II and he did not during his 20-minute-long remarks.
"Why do we come to this place, to Hiroshima? We come to ponder the terrible forces unleashed in the not so distant past. We come to mourn the dead ... their souls speak to us and ask us to look inward. To take stock of who we are and what we might become."
In the Hiroshima museum's guest book before his speech, the President wrote that he hoped the world will "find the courage, together, to spread peace, and pursue a world without nuclear weapons."
A somber Obama spoke after laying a wreath on the museum's cenotaph alongside Japanese Prime Minister Shinzo Abe.
During the speech, the park was silent except for a circling helicopter, chirping birds and camera shutters.
Obama said there is a "shared responsibility" to look into the "eye of history" and ask what must be done to prevent another nuclear weapon being used.
He urged that the world make moral progress alongside its remarkable scientific advancements.
"The scientific revolution that led to the splitting of an atom requires a moral revolution as well," Obama said. "That is why we come to this place."
The President called for an end to senseless wars, even as he reflected that violence has existed throughout human history.
"The world war that reached its brutal end in Hiroshima and Nagasaki was fought among the wealthiest and most powerful of nations," he said.
"Those civilizations have given the world great cities, magnificent art, thinkers that advanced ideas of harmony and truth, and yet the war grew out of the same base instinct for domination. Conflicts can cause conflicts among the simplest of tribes."
Obama closed his remarks by saying, "The world was forever changed here but today the children of this city will go through their day in peace. What a precious thing that is. It is worth protecting."
Obama's visit to the bomb site was at least six years in the making inside the White House, and follows a visit by Secretary of State John Kerry last month.
The President's American delegation at the site Friday included National Security Advisor Susan Rice, U.S. Ambassador to Japan Caroline Kennedy, advisor and speechwriter Ben Rhodes, and others.
Over 100,000 Japanese men, women and children, thousands of Koreans, and a dozen American prisoners of war died in the bombing.
Following his speech, the President met with survivors of the bombing. He shared an emotional embrace with Shigeaki Mori, a 79-year-old survivor who worked for four decades to gain official recognition of the 12 Americans killed in the bombing.
Before the event, another survivor, Sunao Tsuboi, said he "never imagined (the President) would come while I am alive."
"We do not need apologies," Tsuboi added.
"I hope that he will present in Hiroshima what is good for the happiness of humankind. I would like to join hands with each other through the power of reason and beyond hatred."