With a two-point lead at the summit, Medeama look likely to claim the bragging rights. But things are not that simple as the Yellow and Mauves will have to register an away victory over wounded Hearts of Oak to secure the spot. Without a win in their last three league games, the Phobians occupy the 12th position amid calls for head coach Henry Wellington to quit.
Second-placed Ashgold, likewise, face a tall order, with a trip to tenth-positioned Berekum Chelsea on the cards. Known for their fighting spirit at home, the Blues are sure to come blazing on all cylinders.
Allies, who tie Ashgold on points, meanwhile, play away to debutants Karela United, who occupy the fifth spot.
Dreams FC - fourth on the log - and second-from-bottom Ebusua Dwarfs will square off against each other at Dawu.
At the Nana Fosu Gyeabour Park, seventh-placed Wafa will play as guests to Bechem United, who fell 1-0 away to Aduana Stars in midweek.
With just one win this season, bottom-placed Wa All Stars are hoping to end the first round on a good note when they welcome newly-promoted Eleven Wonders to the Malik Jabir Park.
And at the Nduom Sports Stadium, eighth-placed Elmina Sharks will face Liberty Professionals, who have four wins to their name thus far.