The Blaugrana can open up a six-point lead over the capital club with victory in the first Clasico for both sides' coaches
The Catalan giants last won a league fixture against Real Madrid in December 2011, as they came from behind to win 3-1 in the Spanish capital.
And although Copa del Rey and Supercopa wins have since followed, Barca will be determined to end a run that has seen them take just one point from their last three league meetings with Madrid.
Gerardo Martino's table-toppers are the only side to avoid defeat in La Liga this term, having recorded eight wins and one draw.
They were held to a goalless stalemate at Osasuna last week but will hope a return to Camp Nou - where they have won their last 19 Liga matches - helps them return to winning ways.
Real Madrid sit third in La Liga, three points adrift of Barca, with their only loss of the season coming against neighbours Atletico Madrid last month.
Both sides have new stars keen to make an impact in their first Clasico - Neymar, Bale, Isco and Asier Illarramendi - while coaches Martino and Carlo Ancelotti will also experience their first taste of Spain's fiercest derby.
While much attention will focus on the impact of the likes of Neymar and Bale - the latter having returned from a back injury against Malaga on Saturday and confirmed by Ancelotti as fit to feature - Cristiano Ronaldo and Lionel Messi are more than likely to steal the show.
Widely regarded as the two best players on the planet, both have made an outstanding start to the current campaign, with Ronaldo's brace in a 2-1 Champions League win over Juventus on Wednesday taking him to 15 goals from 12 appearances this season.
Four-time world player of the year Messi, meanwhile, has 12 goals in nine outings.
Real will be without midfielder Xabi Alonso, despite him returning to training following a broken foot, while Barcelona defender Jordi Alba (hamstring) will also miss the fixture.
Historically, Real Madrid have shaded the clash, winning 90 of the 224 competitive matches, with Barcelona winning 86.
Ancelotti will be hopeful that his side can lenghten that statistic on Saturday as Real bid to go level on points with their rivals and claim the early Clasico bragging rights this season.