Dozens of heavily armed soldiers and police patrolled the streets, where Al-Qaeda-affiliated Shebab militants regularly carry out bombings and killings.
Ministers from Djibouti, Ethiopia, Kenya and Uganda -- who have contributed troops to the 22,000-strong African Union force in Somalia -- are all taking part in the one-day meeting, organised by the regional IGAD bloc, the Intergovernmental Authority on Development.
Held in a heavily guarded hotel near the main government district in Mogadishu, it is one of the largest and highest profile meetings in the capital for years.
Key issues include security and political reconciliation within the Horn of Africa nation, riven by conflict since 1991.
"This is an important regional event, which is taking place in Somalia for the first time in 28 years," Somali President Hassan Sheik Mohamud said.
"IGAD is a guest of the Somali people... so let us prove to the world we can do this," he said in a televised speech to the nation.
Leaders including UN chief Ban Ki-moon have visited Mogadishu in recent years, but important visitors rarely leave the fortified walls of the airport zone to travel on the dangerous city streets.
"We are very happy that Mogadishu is secure enough to host such an international conference," said Abdirahman Duale Beyle, Somalia's acting foreign minister.
The Shebab have also carried out attacks across the wider east African region.
The talks come after Somalia's parliament last month endorsed Omar Abdirashid Ali Sharmarke as prime minister, following bitter infighting and a falling out between the president and the previous premier.
The United Nations, the United States and the European Union -- key backers of Somalia's fragile government -- all warned that power struggles were a damaging distraction for the country.
Much of Mogadishu was in lockdown on Saturday.
"They are complicating life for ordinary residents. Mogadishu is not yet ready to host international meetings," said Ahmed Suleiman, a resident of the coastal city.
"Every important street is closed and that is the only thing they can do to secure the conference."