"The people of Egypt have spoken. Their voices have been heard and Egypt will never be the same," the president said. "By stepping down, President Mubarak responded to the Egyptian people's hunger for change, but this is not the end of Egypt's transition. It's the beginning."
Obama praised the protesters and their peaceful demonstrations that have rocked the country for the past 18 days.
"Over the last few weeks, the wheel of history turned at a blinding pace," he said.
The president called on Egypt's new leadership to lift the controversial emergency law that has been in place almost continuously since 1967 and gives the government far-reaching powers at the expense of judicial review and civil liberties. He also urged a peaceful and constructive transition to free and fair elections.
Egyptians celebrated late into the night. People streamed into Cairo's Tahrir Square dancing, honking car horns and waving flags. Fireworks were shot off in the square that has become the heart of the uprising.
As Mubarak's long-awaited announcement was made earlier byVice President Omar Suleiman, crowds erupted into loud cheers, chanting "Egypt is free, Egypt is free."
Watch a special, one-hour edition of "Nightline: Revolution Day," anchored by Terry Moran live from Cairo, at 11:35 p.m. ET.
"My fellow citizens. In this difficult time that the country is going through, President Mohamed Hosni Mubarak has decided to relieve himself of his position as president and the Supreme Military Council has taken control of the state's affairs. May God protect us," Suleiman said in a somber one-minute announcement.
The military's spokesman also went on state television to thank Mubarak for his service and said it is reviewing the situation. Saluting those who have died in the nearly three weeks of protests, the military hailed the "martyrs" and said the army will guarantee that the demands of the Egyptian people be met.
He reiterated that the army is not a substitute for the legitimacy the people want and that the military will announce concrete steps soon.
Mubarak, who ruled for 30 years, is the second Arab leader forced to quit by a remarkable populist and largely peaceful uprising. Last month, Tunisia's president Zine al-Abidine Ben Ali resigned and left the country in the face of massive street protests against his regime.
Egypt's high military council, which has taken over the country, is headed by Defense Minister Mohammed Hussein Tantawi. He was made deputy prime minister just two weeks ago in an effort to appease protesters, and visited Tahrir Square during the demonstrations.
"Welcome back Egypt," tweeted Google executive Wael Ghonim, who became the face of protests since he was detained by security forces last month.
Men, women and children -- many with tears in their eyes -- flooded Cairo's streets as the atmosphere turned from one of determination to pure ecstasy.
"The Egyptian people won," a thrilled Amr Hamadi said.
Hamadi, a 32-year-old factory worker who was celebrating with other protesters near the presidential palace, said, "Egypt will be in 10 years one of the best countries in the world."
"This is the greatest day of my life," Nobel Laureate and opposition leader Mohamed ElBaradei said. "The country has been liberated."
The news has significant implications for the world and the United States. Egypt is one of the United States' closest allies in the region, a key economic partner and only one of two Arab states that recognize Israel.
Though the White House has distanced itself from Mubarak's administration over recent weeks, Mubarak was a close U.S. partner, helping broker peace deals between Israel and Palestine and supporting the U.S. in its wars against Iraq.
Mubarak's resignation was celebrated all over the Arab world.
In Gaza City, hundreds came out onto the streets firing weapons in the air in celebration. Fireworks erupted in Beirut as Mubarak's resignation was announced and people driving by the Egyptian embassy in Amman, Jordan, honked in celebration.
Mubarak, 82, left the presidential palace in Cairo earlier today as the pressure to resign mounted.
Sources told ABC News that Mubarak had gone to an estate he owns in Sharm el-Sheikh, a resort town on the Red Sea about 250 miles from the protests in Cairo. Mubarak told ABC News last week he may eventually retire to the resort town, but vowed never to leave Egypt.
In a sign that the regime was crumbling, Hossam Badrawi -- who was appointed head of the ruling party just days ago -- resigned from his post this morning. Badrawi was widely cited by news outlets on Thursday as saying that Mubarak would step down.
The military also announced on state television that the regime's much hated emergency law will be lifted, but only when the security situation allows. The army also encouraged protesters to leave the streets and return to their homes.
But demonstrators were defiant, filling Tahrir Square again to demand Mubarak's ouster. Thousands more marched toward the state television building, a prime new target for today's protests.
Others converged on the presidential palace, blocking roads leading up to the president's residence. The mood was largely peaceful and celebratory, yet determined, as soldiers and protesters cheered and waved at each other.
Similar scenes played out in the port cities of Alexandria and Mansoura.
The historic event in Egypt coincides with the 32nd anniversary of the Iranian Revolution which ended the long reign of the Shah. But experts say the two countries differ vastly and the many don't believe the Iranian experience will be relived in Egypt.
Today's celebrations were in sharp contrast to sullen anger that took over the protesters on Thursday night when Mubarak addressed the country, but stated that he would not step aside. Instead of accepting his announcement, protesters renewed their demonstrations today and the president was soon gone.
ABC News' Jake Tapper, Brian Hartman and Jim Sciutto contributed to this report.