Barra, 51, currently executive vice president for global product development, purchasing and supply chain, will assume the post on January 15.
The announcement came just one day after the US Treasury sold its last shares in General Motors, closing the books on a 2008 bailout executed amid the financial crisis. GM and fellow US automakers Ford and Chrysler have gained on surging auto sales throughout 2013.
Barra has worked at GM for 33 years, rising through a series of manufacturing, engineering and senior staff positions. GM, in a statement, called her "a leader in the company's ongoing turnaround."
An engineer by training, Barra has also served as vice president of global human resources, where she was credited with shaking up a corporate culture that had depressed profits and innovation.
Her GM-heavy background contrasts with Akerson, who joined GM as chief executive in 2010 after working on buyouts for investment firm The Carlyle Group.
Tuesday's announcement unveiled a series of other significant executive changes, including news that board member Theodore Solso would succeed Akerson as chairman.
Dan Ammann, currently executive vice president and chief financial officer, will become president and assume responsiblity for regional operations around the world. The global Chevrolet and Cadillac brands will report to him. A replacement as CFO will be named later.
Akerson, 65, accelerated the succession plan by several months after his wife was recently diagnosed with "an advanced stage of cancer," the company said.
GM shares were off 0.4 per cent in early trade. Shares have risen steadily over the last 12 months.
Analyst reports released after the US Treasury announced it had sold its remaining equity stake in GM said the shares were primed to rise further thanks to improving products and the anticipation of a corporate dividend and share buyback programme.