Interim coach Maxwell Konadu's side currently top the standings by two points from Togo, with Uganda a place further back with four points to their name.
Victory for Konadu's men will guarantee them a spot at the tournament in January and February, although, following the recent decision by CAF to strip Morocco of the competition, a host for AFCON 2015 has not yet been decided.
Konadu will be without Asamoah Gyan - a scorer in Ghana's last three qualifiers - and Juventus' Kwadwo Asamoah due to injury, but has handed a first senior call-up to forward Emmanuel Osei Banahene.
It is likely that Saturday's clash will be the penultimate fixture of Konadu's brief interim reign, with Avram Grant lined up to take over following Kwesi Appiah's departure after the World Cup.
The former Chelsea boss and Spaniard Juan Ignacio Martinez are frontrunners for the post, with Grant currently leading the way.
"In terms of ranking, our preference is Mr Avram Grant and Juan Ignacio Martínez is second choice," Ghana FA president Kwesi Nyantakyi told the media recently.
"We will engage him on the details of the job requirement and expectations which will span from remuneration and conditions of service etc.
"If we reach an agreement with him then we will appoint him as coach, if not then we will move to our second choice."
Ghana round off their qualification campaign against Togo next week, while Uganda face Guinea, with Milutin Sredojevic's side still in the running for automatic qualification.
A win in Kampala could move them second and would certainly improve their chances of progressing as the best third-place team as they seek to feature in their first AFCON since 1978.
However, Sredojevic is anticipating a tough fixture against the four-time African champions.
"Ghana is not the team you can threaten. In recent years travelling across Africa they have only lost once by accident to Zambia," he said, having seen his side run out 3-0 winners over Ethiopia in a recent friendly.
"We are playing a great team, one of the greatest African teams, but we will give our best.
"I want to call it an epic clash, one we really want to get the best out of and look forward to qualifying for the Africa Cup of Nations."
