Arthur Zwane's side are currently in sixth position on the league standings, but just one point and one place better off than Rise and Shine, with just two games of their season remaining.
Chippa United, Kaizer Chiefs, and Marumo Gallants are all just two points further down, leading Zwane to describe this match as a must-win six-pointer.
While Usuthu managed a 1-0 win over Golden Arrows last time out, Polokwane were held to a 1-1 draw with SuperSport United.
Speaking ahead of the match, Zwane said on IOL: "For me, this is the most important game of our season. It's like a cup final for us.
"It's a six-pointer. We are playing against a team that has got one game in hand. We are only leading them by a one-point difference.
"We know that the only time we can be able to consolidate our position for now is to get maximum. It's a fact. All the players are aware of that.
"We have to face the fact that we have let ourselves down on a number of occasions this season.
"So, it's high time we turn things around. We need to show character in this game."
Speaking last month about his side's ambitions this season, City head coach Phuti Mohafe said there is no limit to how high his side could dream, as they battle for one of the continental spots.
"Anything is possible in life, so if that appears to happen then let it be. Let’s go and fight as Polokwane City," he explained.
“No one can do that if we can't do that and we will never know, if we can't try it so rather go and try. We see where we fail and we see if we progress.
“Honestly speaking, last season we surprised ourselves when we qualified for the top eight. Even now, we are so surprised that we fighting for the third spot and I think with us being there that triggers the mentality of saying you can do it [qualify for CAF], then why not, let's try to fight for it."