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'
|Doyle to join Rapids by month´s end|
|MLS Preview: Red Bulls, City to contest first New York derby|
|Real Salt Lake 0 Los Angeles Galaxy 0: Goalkeepers dominate after lightning delay|
|Copa Libertadores Review: Guarani, Sao Paulo in box seat|
|Subotic wants Europa League spot|
|Ligue 1 Preview: Cabaye challenges leaders PSG|
|Bayern ´threw the game away´ against Barcelona - Boateng|
|Sevilla favourites tag motivation for Fiorentina - Montella|
|Cuadrado needs time - Bacca|
|Guardiola: Bayern didn´t lose because of Messi|
|Luis Enrique hails team performance after Messi masterclass|
|Muller hopeful of second-leg fightback in Munich|
|Ribery set to miss Bayern´s second leg with Barca|
|Messi is impossible to describe, says Mascherano|
|Barcelona 3 Bayern Munich 0: Messi lives up to Guardiola´s billing to put Barca on brink of final|
|Spanish federation to suspend all competitions from May 16|
|AFC Champions League Review: Jeonbuk cruise into last 16 but Seongnam crash out|
|McClaren reiterates commitment to Derby amid Newcastle speculation|
|League One play-offs preview: Grayson grateful for Preston´s second chance|
|Belfodil agrees Parma contract termination|
|Sevilla still on track - Emery|
|Duff has Upton Park red card overturned|
|Alexis Sanchez can be as good as he wants - Zamorano|
|Torino 0 Empoli 1: Padelli howler proves costly|
|Real Madrid top Forbes list for third straight year|
|Arnesen backs ´champion´ Van Gaal for success at United|
|McCarthy robbed at gunpoint|
|Paris Saint-Germain v Guingamp: Champions out to pile pressure on Lyon|
|Benitez agent to meet with De Laurentiis|
|Chelsea´s ´boring´ style not an issue - Arnesen|
|Ramos laments poor Turin display|
|Southampton to place trust in academy - Reed|
|Bale not listening to failed managers - agent|
|Bigirimana believes relegation could be good for Newcastle|
|Chelsea still hungry for Liverpool win - Matic|
|Bournemouth to invest in players before stadium|
|Police visit Sports Direct over Rangers investigation|
|Guard of honour should spark Liverpool - Lallana|
|Liverpool to sign teenage Portuguese star|
|Thiago would´ve stayed at Barca under Pep|
|Copa Libertadores Review: Tigres advance to quarters|
|Houston Dynamo 0 San Jose Earthquakes 1: Kinnear claims triumphant Texas return|
|Martinez: Everton got carried away during unbeaten run|
|Neymar has flourished with captaincy - Dunga|
|A-League Preview: Victory, City to meet in biggest Melbourne derby|
|Ramos: Real Madrid in box seat|
|´Bale gave Real nothing´ - Keane|
|Hill backs Ramsey for QPR job|
|Ancelotti confident of Real revival|
|Allegri rues late Llorente miss in Juve triumph|
|Juve sent a warning - Pirlo|
|Inverness Caledonian Thistle 2 Dundee United 1: Ofere and Williams keep European dream alive|
|Juventus 2 Real Madrid 1: Spot-on Tevez earns first-leg lead|
|Sturridge hip surgery a success|
|Coloccini calls for unity as Newcastle target survival|
|Doumbia cleared to make Milan trip|
|Harper calls for Hull unity|
|Guardiola not distracted by Barca homecoming|
|No defence can stop Barca star Messi - Guardiola|
|Neuer ready to face Barca strike trio|
|Napoli v Dnipro: Benitez seeks to make experience count|
|Jones ready for United return|
|Injury rules Oscar out of Brazil´s Copa squad|
|Mazinho proud ahead of Barca v Bayern contest|
|Sevilla v Fiorentina: Kolodziejczak confident ahead of semi-final test|
|Skipper Soriano set for Villarreal return|
|Martinez wary of Pienaar risk|
|AFC Champions League Review: Holders Western Sydney out due to last-gasp Seoul winner|
|Barca focused ahead of Pep return - Luis Enrique|
|Messi has ´no problem´ with Luis Enrique|
|Relegated Tranmere appoint Brabin|
|Ujah agrees Werder transfer|
|Magath backs Guardiola to remain at Bayern|
|Mathieu out of Bayern clash|
|Burnley appeal Duff dismissal|
|Setif drawn in Algeria-heavy Champions League group|
|Terry calls for new Drogba deal|
|Saul agrees bumper Atletico deal|
|Arsenal need to finish season strongly - Wenger|
|New Bilbao deal for Gurpegi|
|Pepe puts Morata friendship aside for Champions League match-up|
|Terry: Too long between titles|
|Hazard can be as good as Messi, Ronaldo - Fabregas|
|Carlisle ´deeply ashamed´ about suicide attempt|
|Tevez planning to win Champions League with Juve|
|Blatter ´knows absolutely nothing´ - Maradona|
|Allegri: Ancelotti a smart man|
|Sunderland academy coach to manage Oldham|
|Primeira Liga Review: Braga secure Europa League berth|
|Bruce backing Hull to respond against Burnley|
|Almeria 2 Celta Vigo 2: Bifouma, Zongo inspire hosts´ comeback|