The appointments on Thursday by Muhammad Naji al-Otari mean more than half the faces in the new government, dominated by members of the country's ruling party, are new.
Officials said Ghassan al-Rifai, who was minister of economy and foreign trade in the last government, would take on a new portfolio expanded to include domestic trade and supply.
Former Deputy Prime Minister Muhammad al-Husayn was appointed finance minister, and Ahmad al-Hasan, a former ambassador, replaced Adnan Omran as information minister.
Syrian Foreign Ministry spokeswoman, Bouthaina Shaaban, was appointed minister of expatriates, the officials said.
President Bashar al-Assad accepted the resignation of former Prime Minister Muhammad Mustafa Mero last week and appointed Otari, a former parliamentary speaker, to head a new government.
It was the second reshuffle that al-Assad - who took office in 2000 vowing economic and political reform - has carried out since he became president.
It coincides with mounting US pressure on Syria over its support for Lebanon's Hizb Allah and Palestinian resistance fighters, as well as accusations of meddling in Iraq to undermine the US-led occupation of the country.