Midfielder Gimenez put Cruz Azul ahead in the first half at the Azul stadium, putting away midfielder Hugo Droguett's cross from the left.
Argentine Gimenez scored again with a shot from outside the box and compatriot Villa also got on the scoresheet with a header from a corner as Cruz Azul scored twice in quick succession midway through the second half.
Cruz Azul are third in Group Three with 24 points from 14 matches and still on course to go through at least as one of the two best third-placed teams.
The top two teams in each of the three groups plus the next two best-placed teams in the overall standings after the 17-match round-robin phase qualify for the quarter-finals.
The victory was sweet revenge for Cruz Azul after they lost to Monterrey in the semi-finals of the Concacaf Champions League last week.
Pumas UNAM lead Group Three with 29 points after a 0-0 draw away to Atlas. Morelia are second with 27 having beaten bottom team Chiapas 2-1 on Tuesday.
Tigres UANL lead Group One with 26 points after beating Pachuca 4-2 with two goals from Chilean striker Hector Mancilla. Guadalajara are second with 24 after a 2-1 win at Toluca and Monterrey third on 21.
Santos Laguna, runners up to Monterrey in the Apertura championship in the first half of the season, crushed Puebla 4-0 as they continue their recovery from a dismal start to the Clausura including a change of coach.
With Argentine Diego Cocca at the helm they climbed to fourth in Group One with 17 points.
Atlante opened a three-point lead over America in Group Two with a 4-1 away win over Queretaro. Atlante have 22 points and America 19 in a tight group in which there are only six points between the leaders and bottom team Pachuca.
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