Australia and New Zealand by next year.
It also said China's Great Wall Motors had agreed to buy its manufacturing plant in Thailand.
The announcement comes three years after GM ended manufacturing in Australia.
In a statement posted on GM's website, chief executive Mary Barra said: "I've often said that we will do the right thing, even when it's hard, and this is one of those times."
The statement did not say how many jobs would be lost as a result of the move but reports suggest it will mean up to 600 layoffs.
In response to the news, Australian Prime Minister Scott Morrison said: "I am disappointed but not surprised. But I am angry, like I think many Australians would be.
"Australian taxpayers put millions into this multinational company. They let the brand just wither away on their watch. Now they are leaving it behind," he added.
GM President Mark Reuss said the company had explored ways to keep the Holden brand but had decided that it would cost too much to remain in the "highly fragmented right-hand-drive market".
It comes as GM is accelerating its exit from unprofitable markets as it focuses on the US, China, Latin America and South Korea.
The move will end 160 years of the Holden name's association with Australia. The company was founded as a saddle maker in South Australia in 1856 before it started building vehicles in 1908.
Holden was bought by GM in 1931, beginning their 89-year history as a combined entity.
The hashtag #RIPHolden is trending on Twitter as people post pictures and memories of the much-loved Australian brand.
Late last year the company also said it would stop selling its most iconic model the Commodore after more than four decades.
At the end of 2013 Holden announced that it would halt production in Australia and start importing vehicles from its overseas plants. GM said a strong Australian currency, high manufacturing costs and a small domestic market were among the reasons behind its decision.
The ending of Australian production of Holdens in 2017 resulted in nearly 2,900 job losses.