De Nigris, whose Greece-based footballer brother Antonio died of a heart attack three weeks ago, scored either side of half-time in the semi-final first leg at the Tecnologico stadium in Monterrey on Thursday.
The former Mexico under-20 forward headed Monterrey in front from Chilean Humberto Suazo's free-kick and increased their lead when he took a pass from midfielder Luis Perez, turned two defenders and shot past advancing keeper Alfredo Talavera.
The Monterrey-born De Nigris narrowly missed out on a hat-trick three minutes from time when he was put through by Suazo, leaving two defenders in his wake, but shot wide.
"I know I have my brother by my side, he's the one giving me strength and I will have him with me all my life," De Nigris was quoted as saying on Monterrey's official page of the website www.terra.com.
De Nigris also scored against America in the first leg of their quarter-final, his first match after his 31-year-old brother's death. Monterrey won that match 1-0 and the second leg 1-1 to progress.
"We lost the chance of a well-deserved third goal but we still did a good job," Perez told Televisa.
Cruz Azul, who began the knockout phase as favourites to reach the final with Toluca, drew 0-0 at Morelia in the first leg of their semi-final on Wednesday.
The return is on Saturday while Monterrey visit Toluca on Sunday.
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