Through 15 rounds, Guillermo Vazquez's men are two points clear at the helm from rivals Toluca, who reduced the gap last weekend after Cruz Azul were held to a draw at home to Pachuca.
The top two sides have 10 wins each, with Cruz Azul's three draws the difference - and they can boot five points clear before Toluca play on Saturday.
Cruz Azul, though, will have to turn around a poor recent record in Morelia, which has seen them fail to win there in their past seven attempts.
Morelia sit in mid-table on 18 points, just one above third-last Monterrey, and only three off sixth-placed Pachuca.
Toluca are on the road at Atlas, also on 18 points, with Jose Cardozo's men high on confidence after holding Cruz Azul to a scoreless draw in the first leg of the CONCACAF Champions League final in Azul.
It was their third unbeaten result in succession, after their semi-final second leg win over Alajuelense was followed by a 2-1 league win over Leon.
Toluca's recent record at Atlas' Guadalajara home is positive, with two wins in their past three trips there - including a 3-1 win on their last visit in September 2012.
Also on Saturday, fourth-placed America host Queretaro looking to improve on their horrid record at their Estadio Azteca of late.
In front of their home faithful, America have just one point from their past five, with their brilliant away record of late - 10 points from four trips - has held them in good stead in the table.
Santos Laguna (third) welcome Chiapas to Torreon, having won their past five home games in all competitions, albeit with just one clean sheet in that run.
Pachuca host Puebla, Veracruz are on the road at Monterrey while Leon accommodates Tigres UANL and Atlante are at home to Tijuana.
On Sunday, Pumas UNAM - fifth on 22 points - take on eighth-placed Guadalajara, with the latter able to usurp their opposition on the table with a victory.
