Jolie spoke at Jordan's largest camp for Syrian refugees, which she toured as special envoy for the United Nations refugee agency.
"I appeal to the world leaders—please, set aside your differences, unite to end the violence, and make diplomacy succeed," she told reporters, drawing attention to the U.N.'s World Refugee Day.
Jolie is returning to her humanitarian work after announcing last month that she had her breasts removed after discovering she has an inherited genetic mutation that puts her at high risk of breast and ovarian cancer.
Her visit to Zaatari camp was her first visit public appearance with the United Nations refugee agency since the double mastectomy.
The actress said that by the end of this year, "half of Syria's population—10 million people—will be in desperate need of food, shelter and assistance."
"The lives of millions of people are in your hands," said Jolie, who wore a black T-shirt and pants under the scorching desert sun, as billows of dust were kicked up by the wind. "You must find common ground."
In her news conference under a tent in Zaatari camp, she said that refugees are "often forgotten and frequently misunderstood."
"They are regarded as a burden, as helpless individuals, or as people who wish to move to someone else's country," she said.
"That is not who they are," she added somberly. Rather, refugees are people to invest in, "who will one day rebuild their countries, and a more peaceful world for us all."
Jordan hosts more than half a million displaced Syrians, including 185,000 in Zaatari, which has become Jordan's fourth largest populated city.
Inaugurated last July, Zaatari is the world's second largest refugee camp, according to the United Nations High Commissioner for Refugees. The largest according to the UNHCR is Dadaab camp in Kenya, which houses 463,000 Somali refugees.
Jolie visited Zaatari along with UN High Commissioner for Refugees Antonio Guterres and Norwegian Foreign Affairs Minister Espen Barth Eide.