Cardozo's header after 55 minutes from a Melgarejo cross and a volley 14 minutes later settled the Group G encounter and lifted the Portuguese side above their Russian rivals by a point to set up a second-place tussle with Celtic later this month.
Cardozo also hit the bar from the penalty spot after Nicolas Pareja was shown a red card 14 minutes from time as the home side avenged their 2-1 defeat in Moscow two weeks ago.
Benfica now have four points and Spartak three behind group leaders Barcelona who have nine. Celtic, who defeated Barcelona 2-1 on Wednesday, are on seven.
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