Islamic State will also top the agenda. US President Barack Obama will host a counter-terrorism meeting, with over 100 countries invited, that will address Islamic State, foreign terrorist fighters and violent extremism.
Russian Foreign Minister Sergei Lavrov will chair a high-level UN Security Council meeting on counter-terrorism.
But before the marathon of speeches in the 193-member General Assembly starts, Pope Francis will address the United Nations on September 25 ahead of a three-day summit with more than 150 world leaders that will formally adopt a global sustainable development agenda for the next 15 years.
"General Assembly high-level week is always known as diplomatic speed-dating, but I think this year is breaking records," said the US ambassador to the United Nations, Samantha Power. She said it was believed to be the highest number of world leaders attending in UN history.
The leaders making rare appearances for the United Nations' 70th anniversary include German Chancellor Angela Merkel, Cuban leader Raul Castro and Russian President Vladimir Putin.
The United Nations was established as the successor to the failed League of Nations in 1945 after World War Two to prevent a similar conflict from occurring again.