The Aguilas kept hopes of qualification from the group stage alive with a victory over their Russian opponents, as their Paraguayan striker proved the difference
Cardozo wasted no time in leaving his mark on the game after being introduced at the break, as he scored two goals in quick succession, the first a powerful header from close range, and the second a well-taken half-volley from 10 yards out.
Despite both teams being guilty of conceding a number of free kicks in the opening 10 minutes the home side was clearly on top as the Spartak defense struggled to deal with the vibrant play of Ola John and Melgarejo playing on the left-hand side for Benfica.
The Aguias continued to dominate possession, and very nearly took the lead in the 22nd minute, only for Salvio to blast a shot into the side netting after the ball fell invitingly to him inside the Spartak penalty area.
Rodrigo came within inches of making it 1-0 to the home side in the 40th minute, but could only look on in anguish as his devilish free kick from the right flew just wide of Rebrov's right-hand post with the Spartak goalkeeper well beaten.
Jorge Jesus made an attacking change at the break, bringing on Cardozo for Rodrigo, yet it was Spartak that came close to taking the lead early in the second half through Bilyaletdinov. The attacker wasted his second chance of the evening though, firing straight at Artur after some fine build-up play involving Ari and Dmitriy Kombarov.
After having one finely-taken effort ruled out for offside just minutes after being introduced, Cardozo then gave Benfica a legitimate 1-0 lead with a close range header in the 55th minute. Melgarejo was instrumental with the assist as he ghosted into the box on the left before lifting a perfect cross on to the head of the Paraguayan striker, who then headed the ball downwards past Rebrov and into the back of the net.
Jesus' decision to bring on Cardozo continued to prove an inspired choice as the attacker then struck the crossbar in the 66th minute with a firm header after connecting well with John's inviting corner from the left.
That same duo combined again just moments later to make it 2-0 to Benfica, with Cardozo adjusting his body well to meet John's bouncing cross with his left foot and divert the ball into the back of the net from 10 yards.
Spartak's evening went from bad to worse in the 76th minute as Pareja was dismissed for an awful challenge on Cardozo inside the penalty area. However the striker's chance to complete his hat trick eluded him as his firmly-struck spot-kick was tipped on to the crossbar brilliantly by Rebrov.
Cardozo had one final chance to make it three goals in 45 minutes late in the game, but after racing through on goal he poked an effort just wide of Rebrov's right-hand post under pressure from Juan Insaurralde.
Benfica's impressive victory reignites its hopes of progressing from Group G, and increased its unbeaten run of home games against Russian opposition to six.