The Estadio Azteca will host around 100,000 fans as Liga MX leaders América look to extend their six-point advantage at the top of the league.
Guadalajara have been playing poorly recently, drawing four of their last five games, but will travel to the Azteca with fresh memories of the 1-0 friendly victory over their rivals America in July.
It shapes as a match that could be decided by both teams' young guns.
For América, 22-year-old Raul Jimenez has struck six goals in nine games, while 24-year-old Marco Fabian has scored three goals in nine games for the visitors, however he has only started in five of those games.
Already 20 points behind América after 11 games (both teams have a game in hand over the rest of the competition), Guadalajara's chances of winning the title appear to be slim, but a win over their arch-rivals could kick start their season.
In other games, Morelia host Chiapas on Saturday hoping to put some daylight between themselves on Chiapas who sit on equal points and goal difference in sixth place.
Tijuana will look to turn around their recent poor results against Querétaro who have also struggled lately after a strong opening 10 games.
On Sunday, Toluca will face a trip to Tigres hoping to capitalise on their good form in the league and move ahead of Leon who sit two points above them.
Veracruz will once again rely on the goals of league top-scorer Angel Reyna when they travel to Pachuca.
Bottom-placed Atlante will welcome Monterrey as both teams look to recover from losses last weekend.
Leon will look to bounce back from a recent loss to Cruz Azul when they welcome Puebla, with the former America's closest rival to the title.
Cruz Azul themselves welcome Atlas who have only managed four draws from their last five outings and have conceded the second most goals of any team this season.
On Monday, Pumas UNAM will be hoping to build on last week's win against Monterrey after a poor start to the season, but will face a stern test as they face fourth-placed Santos Laguna as newly appointed coach Jose Luis Trejo continues to try and turn around the club's fortunes.
|Coach: M. Herrera|
for L. Mendoza 56'
for Paul Aguilar 70'
for R. Sambueza 83'
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