Ms Colonna, 66, is the second woman to lead France's Foreign Ministry after a short stint by Michele Alliot-Marie in 2010.
The seasoned diplomat has held posts in Washington and Brussels, is a former ambassador to Italy and a former secretary of state for European affairs.
She was also spokeswoman for former president Jacques Chirac
Ms Colonna's appointment may signal that President Emmanuel Macron is seeking to appease a diplomatic corps angered by his past accusations of civil servants at times working against the executive.
More recently, Mr Macron's decision to reform the diplomatic career structure has led to their unions calling for a strike next month — only the second in their history.
The reform will scrap a special status for senior Foreign Ministry officials meaning they would fall into a broader civil service pool.
“She will be appreciated at the Foreign Ministry. She will reassure at a time when the ministry is facing doubts, uncertainty and the end of the diplomatic corps,” said Jean de Gliniasty, former ambassador to Russia.
“The Foreign Ministry is not in a good state psychologically.”
Ms Colonna is best known as the late Mr Chirac's spokeswoman, a job she held for nine years, including when France opposed the US-led war in Iraq.
Her experience will also help with continuity regarding the conflict in Ukraine, given London's active support of Kyiv.
She replaces Jean-Yves Le Drian, who had been a minister, first at the defence ministry and then foreign ministry, for 10 years.
She will work closely with former centre-right politician Sebastien Lecornu, a close ally of Mr Macron, who takes over as defence minister, after serving as overseas minister.
Clement Beaune remains as Europe minister.