"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.