Jolie, who has been on more than 60 field assignments during her 21 years with UNHCR, said she wanted to keep working with refugees outside of the global body.
"I will continue to do everything in my power in the years to come to support refugees and other displaced people," Jolie said in a statement announcing her departure.
"After 20 years working within the UN system, I feel it is time for me to work differently, engaging directly with refugees and local organisations, and supporting their advocacy for solutions," she said.
Jolie has been UNHCR special envoy since 2012.
This year, she visited Yemen and Ukraine to meet with displaced people.
The UN high commissioner for refugees Filippo Grandi thanked her for her service, commitment and the difference she has made for refugees and people forced to flee.
"After a long and successful time with UNHCR, I appreciate her desire to shift her engagement and support her decision," Grandi said.
"I know the refugee cause will remain close to her heart, and I am certain she will bring the same passion and attention to a wider humanitarian portfolio."
The UNHCR estimates there have never before been so many people forced from their homes by violence, conflict and persecution.
It estimates that more than 100 million people are currently displaced around the world.
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