Obama accepted a humanitarian award from director Steven Spielberg at the University of Southern California's Shoah Foundation, a Holocaust museum founded by Spielberg after he made the film "Schindler's List."
Obama spoke about a variety of global conflicts including Ukraine, Syria, and the kidnapping of more than 200 Nigerian girls by the Boko Haram Islamist militant group.
"We only need to look at today's headlines: The devastation of Syria, the murders and kidnappings in Nigeria, the sectarian conflicts, the tribal conflicts to see that we have not yet extinguished man's darkest impulses," Obama said.
He expressed alarm about a rising tide of anti-Semitism based on events such as a gunman's attack on two Jewish facilities in Kansas and the distribution of pamphlets in eastern Ukraine that demanded the registration of Jews.
"None of the tragedies that we see today may rise to the full horror of the Holocaust," he said. However, he said "they demand our attention that we not turn away."
"We have to act even where there is sometimes ambiguity. Even when the path is not always clearly lit. We have to try. That includes confronting the rising tide of anti-Semitism in the world," he said.
Obama said Americans must speak out against any rhetoric that threatens the existence of Israel "and to sustain America's unshakeable commitment to Israel's security."
The Shoah Foundation's annual gala featured Bruce Springsteen performing "Promised Land" and "Dancin' in the Dark," and a comedy routine from Conan O'Brien.
At Obama's table were Spielberg, Barbra Streisand and "Schindler's List" star Liam Neeson.