Abdallah Deerow Isaq, the Constitution and Federalism Minister, was killed as he left Friday prayers in the town of Baidoa - seat of the fragile interim Somali government.
"It looks like an organised assassination," Mohamed Abdi Hayr, the Somali information minister said.
"So far we do not know who did it. They shot him as he was leaving the mosque then ran off. Police are chasing the gunmen."
The government was formed in 2004 as the 14th attempt to restore central rule to Somalia since the 1991 overthrow of military ruler Mohammed Siad Barre.
It has been unable to halt the rise to power of the Supreme Islamic Council of Somalia - an Islamist militia that took control of the capital Mogadishu and other towns in June.
Deerow was not among the 18 ministers who resigned from the administration on Thursday, complaining about the government's inability to stabilise the African nation.
Also on Friday, fighters loyal to the Islamist group closed roads around the capital's airport and chased away onlookers while a large cargo plane was unloaded of unidentified cargo.
A similar aircraft landed on Wednesday, and officials from the transitional government accused Eritrea of sending arms to the militants.
Local people said several trucks came to collect the delivery from the airport.
"The Islamists are arming themselves and now we have to wait for fighting," said Abdullahi Ali, a local man.