The Students are oozing with confidence after beating Mamelodi Sundowns 1-0 in their previous league game at home on Monday, with Ben Motshwari scoring the only goal of the match.
This was Wits' second consecutive win in the league, having defeated Highlands Park in Tembisa over the weekend before facing Sundowns.
As a result Wits are now sitting at the top of the log with 51 points from 25 matches. They are only a point ahead the defending champions Sundowns, who are placed second.
The Clever Boys could be without six key players when they face Bucs. Buhle Mkhwanazi, Xola Mlambo, Nazeer Allie and Mogakolodi Ngele are nursing injuries, while Granwald Scott and Daine Klate are suspended.
Wits head coach Gavin Hunt will look to mastermind victory over Bucs in order keep his side at the top of the log as the race for this season's league title intensifies.
Meanwhile, Pirates will be keen to maintain their unbeaten run in the league when they lock horns with Wits in Braamfontein.
The Buccaneers are coming off a narrow 2-1 win over Chippa United in their previous league game at the Orlando Stadium last weekend, with Thamsanqa Gabuza and Thabo Matlaba netting for Bucs.
The win extended their unbeaten run to four matches having recorded two straight draws and a win over Maritzburg United, before taking on the Chilli Boys.
Pirates are now placed eighth on the league table with 31 points from 25 matches. They are only ahead of ninth-placed Lamontville Golden Arrows on goal difference.
Thembinkosi Lorch is expected to miss Bucs' clash with Wits as the attacking midfielder is struggling with a shoulder injury.
Bucs head coach Kjell Jonevret knows that a victory over the Clever Boys will cement their place in the top eight.
In head-to-head stats since 1985, Wits and Pirates have met 62 times in the league.
Bucs have dominated this fixture winning 25 games compared to Clever Boys' 16 victories, while 21 matches have ended in draws.
In their last league meeting, Wits won 2-1 at the Orlando Stadium with Frank Mhango netting a brace, while Happy Jele scored for Pirates.