Leandro Marin got the first goal after 82 minutes and Jonathan Calleri added a second in injury time to ensure that the Buenos Aires side are the only team to win all six of their group games.
The result means Boca, who will receive the top seeding, will play River, who have the weakest record so far and will be seeded 16th.
Boca manager Rodolfo Arruabarrena played down the already mounting excitement over the clash and said the seedings will not matter when the great rivals come head to head.
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"From now on there are no favourites, whoever plays best will qualify," Arruabarrena said.
"Playing against Argentine sides, we know all about them, they are games in which the smallest details will be decisive."
The only other side with a chance of equalling Boca's 100 percent record were Corinthians, who drew 0-0 at home to reigning champions San Lorenzo.
The point guarantees Corinthians a place in the last 16, with San Lorenzo battling it out with Sao Paulo for the second qualifying spot from Group Two.
Uruguayan team Wanderers also qualified on Thursday after beating Venezuelan side Zamora 3-0 to take second place in Group Five behind Boca.liba
Brazil side Internacional moved to the top of Group Four with a resounding 4-0 win that eliminated home side Universidad de Chile.