The Amakhosi assistant boss fills the hot seat left vacant following the sacking of Vladimir Vermezovic on Thursday afternoon.
The Serbian tactician had been under fire for months after failing to bring any silverware to Naturena, although the fourth-placed Glamour Boys are just six points behind PSL leaders Orlando Pirates with seven games left in the season.
The weekend's cup clash against Ea Llo Koto at the Peter Mokaba Stadium will be a baptism of fire for Khuse and his fellow coaching team, with Bafana Bafana and Chiefs legend Doctor Khumalo recalled to the dugout.
"We have an immediate challenge ahead of us, Free State Stars. We are playing against a good team and a very good coach who is very passionate about the game. We will need to do our homework," Khuse told his club's official website.
"We need everyone to be focused and speaking to my colleagues, we agree that the first thing is to restore the confidence of the players and show them that they are all capable of lifting the club to greater heights. We will address the players for the first time this evening (Friday).
He added: "It feels good that the Chairman (Kaizer Motaung) has shown trust in us. We have been there before and all we have to do is to give our best to take the team to the next level.
"I also welcome an opportunity to work with Doctor (Khumalo). We worked together back in 2002/2003 season and recently in the Reserve Team.
"He will bring a lot of experience in the Technical Team having been a player here and gone through coaching courses. We both share the ambition to see the Club at the top."
Having been working hard with Amakhosi's development sides, Khumalo is excited to help uplift the senior team's performances towards the close of the 2011/12 campaign.
"I am humbled to have been given this opportunity by the management to contribute and steer the ship towards the right direction," he claimed.
"I have never left Chiefs and have been doing the same thing in the development structures and the only difference now will be affiliation.
"We immediately need to bring back the special 'Chiefs smile'. Our supporters have a special smile and it is important that they start showing that smile on the stands again.
"The supporters have always been the backbone of the club and it will be important for them to rally behind the team starting on Saturday against Free State Stars."