The appeal, called the "Humanitarian Action for Children 2014" and started Friday, would aid 85 million people, of whom about 59 million are children, UNICEF said in a release.
About $835 million of the aid will go to help children and adults in Syria, which is now in its third year of civil war.
"Children are always the most vulnerable group in emergencies, facing a high risk of violence, exploitation, disease and neglect," said Ted Chaiban, UNICEF's director of emergency programs.
About 40 percent of the aid for Syrians has been earmarked for immunizations, as well as water and sanitation, education, and protection projects.
The aid would also "support the social cohesion and peace-building skills needed to build a more sustainable future," UNICEF said.
Also Friday, the United Nations High Commissioner for Refugees called on the countries around the world to make commitments to offer resettlement opportunities or other forms of admission to 100,000 Syrian refugees in 2015 and 2016, the UNHCR said in a release.
Previously, the UNHCR urged countries to admit 30,000 of the most vulnerable Syrian refugees by the end of 2014. So far, 18,800 refugees have been offered resettlement in 20 different countries.
"UNHCR remains confident that the 30,000 goal will be met by the end of the year through a significant number of submissions to the United States," spokesman Dan McNorton said. "We appeal to the international community to continue providing longer-term solutions for Syrian refugees who are most urgently in need."