Melbourne Victory and Melbourne City will square-off in the 15th Melbourne Derby on Saturday, while leaders Perth are at home to Sydney FC.
Albanian striker Besart Berisha has set the stage for a fierce Melbourne derby after claiming Melbourne Victory are the number one team in the city.
Third-place Victory and local rivals Melbourne City, who are sixth in the standings, will meet in front of what is expected to be a bumper crowd at Etihad Stadium on Saturday.
Victory and City have shared the bragging rights after two derbies this season.
Berisha netted a hat-trick in his first Melbourne derby as Victory ran rampant 5-2 in October, while City were 1-0 winners in December.
Erik Paartalu's 90th-minute header gave City the honours last time around and Berisha is determined to set the record straight in the 15th instalment of the derby.
"We are number one in this town and we have to prove it," Berisha said.
"For us, this is what counts. We need to win this game and I'm going to try everything and the boys are [too].
"It's a special game. I believe, like always, it's going be all navy blue [in the crowd].
"In the last [derby]. I didn't score and this, for me, is not good. I have to focus on this derby and make sure that I don't think about what happened before.
"I have to make sure that I do my job. I'm ready to score goals because it's a special game for the club and the supporters."
While bragging rights are important for Victory (29 points) - 10 point above City - maximum points in round 16 are just as crucial for Kevin Muscat's men as they attempt to keep pace with leaders Perth Glory (33 points).
Victory surrendered a two-goal lead as they drew 3-3 in Perth last round, leaving them four points adrift of the Glory, who are also in action on Saturday.
Glory play host to fifth-placed Sydney FC at nib Stadium.
The fixture could see Slovenian defender Denis Kramar handed his debut for Perth, having arrived from La Liga outfit Getafe on a short-term injury replacement contract during the week.
"It's great to be in Perth, I've never been to Australia before so I'm looking forward to making the most out of this opportunity and being part of the team's maiden premiership aspirations and hopefully a championship" Kramar said.
High-flying duo Adelaide United (29 points) and Wellington Phoenix (28 points) are both on the road in round 16.
Second-placed Adelaide, who welcomed former Real Madrid forward Miguel Palanca to the club during the week, travel to Gosford to face Central Coast Mariners on Saturday.
Wellington - fourth in the table - take on cellar-dwelling Western Sydney Wanderers at Pirtek Stadium on Sunday just days after suffering a late 3-2 defeat to Brisbane Roar.
Roar kick-off the round on Friday as they go travel to Newcastle to go head-to-head with the home-town Jets.