Gerry Dorizas joined Holden as chairman and managing director on 1st March 2014, only months after the company announced it would end local manufacturing in 2017.
Holden said in a statement that Dorizas had resigned with immediate effect to "pursue other opportunities".
GM Holden's chief financial officer, Jeff Rolfs, will assume the role of interim managing director as the company begins a search for its seventh boss since 2003.
A Holden insider said the vision set out by Dorizas to become the country's most popular brand within three years of becoming an import-only business remained "unwavering".
Stefan Jacoby, executive vice president and president of General Motors International, thanked Dorizas in the official statement for his contribution to GM Holden, and said nothing changed.
"The foundation has been built to transform GM Holden in Australia, and we are determined to maintain momentum to continue to push towards our strategic objectives," Jacoby said.
He added that Dorizas had "taken the reins of GM Holden at a difficult period and implemented a number of measures" to transition from manufacturer to national sales company.
Dorizas's tenure isn't the shortest at Holden. Chris Gubbey led the local car maker from 1st July 2007 for just six months before being replaced by Mark Reuss.