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'
|AC Milan 3 Crotone 1 (aet): Bonaventura and Niang extra-time strikes send hosts through|
|Leganes 2 Granada 1: Segunda Division side threaten upset|
|Ligue 1 Review: Leaders Paris Saint-Germain held on the road|
|City thrashing cruel on Hull - Bruce|
|City thrashing cruel on Hull - Bruce|
|Pellegrini: Silva brings style back to City|
|Reaching last four is ´terrific´ - Martinez|
|Lukaku urges Everton to push on|
|FIFA sponsors call for ´independent oversight´ of reforms|
|Stoke City 2 Sheffield Wednesday 0: Potters end visitors´ League Cup run|
|Manchester City 4 Hull City 1: De Bruyne double books semi-final spot|
|Middlesbrough 0 Everton 2: Deulofeu and Lukaku on target in routine win|
|Reus Deportiu 1 Atletico Madrid 2: Third-tier hosts make life difficult for Atleti|
|Amnesty International critical of Qatar, FIFA|
|Angers 0 Paris Saint-Germain 0: Cavani fails to make his mark|
|Ramos: Madrid fight for Undecima every day|
|Silver screen awaits for Vardy?|
|Del Bosque noncommittal on Aduritz form|
|Dybala: Juventus´ slow start normal|
|Koeman confident Southampton can match Liverpool|
|Venezuela stars issue quit threat to FA|
|Moreno agent opens door to Real Madrid offer|
|Herrera: I´m very happy at Manchester United|
|Lars Bender undergoes ankle surgery|
|Delneri takes over at Verona|
|Bellerin: I did not know how to defend until I joined Arsenal|
|Panathinaikos hit with three-point penalty after violence|
|Martial and Depay unhappy under ´selfish´ Van Gaal - Parker|
|Injured Carvajal set to miss Cadiz tie|
|Klopp vows to play strongest Liverpool team against Southampton|
|Ronaldo rested for Copa clash|
|Sanchis implies Neymar provoked Isco kick|
|Benitez: I have no problem with James|
|Luis Enrique plays down Suarez Ballon d´Or omission|
|Sergio Ramos is right - football is cyclical, says Luis Enrique|
|Klopp defends Mignolet amid Ter Stegen rumours|
|Boksic backs Mandzukic to get 20 goals for Juve|
|Neymar hails ´great friends´ Messi and Suarez|
|Chelsea submit planning application for new stadium|
|French sports people need to be exemplary - Valls|
|Moyes: Valencia job has come too soon for Neville|
|Napoli loss ´doesn´t change anything´ for Mancini|
|Ronaldo ´uncomfortable´ as a number nine, claims Madrid great Sanchez|
|Manchester City receive $400m Chinese investment|
|Messi: Ronaldo deserves Ballon d´Or nomination, but I´d prefer Suarez|
|Moyes open to another European gig|
|Everton welcome cup pressure - Martinez|
|Casillas open to MLS move|
|Hughes: Butland going nowhere|
|Milner eyes trophies at ´exciting´ Liverpool|
|Napoli became anxious - Sarri|
|Inter did not deserve to lose - Mancini|
|Messi beats Ronaldo to top prize at La Liga awards|
|Bolton Wanderers 1 Brentford 1: Smith watches on as strugglers snatch point|
|Napoli 2 Inter 1: Higuain at the double as hosts go top|
|Lewandowski: Less pressure on me than Aubameyang|
|Defoe, Larsson to miss Arsenal match|
|Sassuolo 1 Fiorentina 1: Di Francesco´s side extend unbeaten home run|
|Barcelona took ´a step forward´ without Messi - Busquets|
|Unfair to blame Garcia for Roma form - Zanetti|
|Southampton v Liverpool: Returning stars have Ibe in buoyant mood|
|Lewandowski´s five-goal haul recognised for four records|
|Barcelona v Villanovense: Holders get second crack at minnows|
|Verona sack Mandorlini|
|Valencia confirm Nuno departure|
|Premier League clubs reveal agent fees|
|Stoke will not underestimate Sheffield Wednesday – Hughes|
|Robben wants Guardiola to stay at Bayern|
|Aguero allays foot injury concerns|
|Cadiz v Real Madrid: Pepe calls for hard work in Andalusia|
|Bolton confirm players have not been paid for November|
|Neville takes Valencia training following Nuno resignation|
|Mihajlovic targets Coppa Italia triumph|
|Garde confident Villa will survive|
|Everton to make late call on Barry and McCarthy|
|Davids: Messi is an anomaly but Ronaldo just an athlete|
|Simeone open to January signings following Tiago injury|
|Messi leads nominees for Puskas Award|
|Hummels defends himself after media criticism|
|Messi, Ronaldo and Neymar nominated for Ballon d´Or|
|Luis Enrique, Guardiola and Sampaoli up for World Coach of the Year|
|Chelsea about the team, not just Costa - Ivanovic|
|Kuyt open to Feyenoord extension|
|Barcelona lodge complaint over ex-Madrid duo´s Neymar comments|
|Davies wants Manchester City quarter-final to get crazy|
|Ribery ordeal is over – Rummenigge|
|Smalling: Vardy run opens door to non-League hopefuls|
|Bender relieved to end Dortmund losing streak|
|Mata: Manchester United have six finals in December|
|Vardy reveals painful road to Premier League record|
|Pardew urges Newcastle to back McClaren|
|Russian clubs banned from signing Turkish players|
|Klopp expects Coutinho to face Southampton|
|Valverde: Let´s hope Barcelona don´t sign Aduriz|
|De Bruyne relishing link-up with Silva|
|´Crazy´ Munich could convince Guardiola to stay|
|Defiant Garcia refuses to resign despite Roma slump|
|Monk confident Swansea can turn the corner|
|Bellerin: Arsenal can cope without Sanchez|
|McClaren: Newcastle not panicking|
|Klopp delighted with Sturridge, Henderson returns|
|I wouldn´t swap Lukaku for Vardy - Martinez|
|MLS Review: Timbers, Crew to meet in final|
|Nuno saddened by Valencia departure|
|Morata will become a key player - Allegri|