The address which is expected to last 15 minutes is expected at 15:00 GMT. It would be the third by President Mahama.
The first was in 2012 after he was sworn in to complete the four year term of the late President J.E.A. Mills.
When he mounts the podium at the UN headquarters to address the world, he would be touching on critical events not only at home but also those in other parts of the world.
President Mahama who is the chairman of ECOWAS is also expected to touch the Ebola disease situation in West Africa.
He recently toured three countries faceted by the disease – Liberia, Sierra Leone and Guinea.
His spokesman, Mr Ben Dotsei Malor said, the President was expected to inform his colleague world leaders what he saw on the ground and call for the end to the isolation of the countries.
Meanwhile President Mahama chaired the South-South Energy initiative presidential round table discussion held on the sidelines of the UN general assembly last Tuesday.
It was meant to push the agenda to improve the energy situation in the developing countries to facilitate development.