Independiente were awarded a 3-0 victory just hours before Tuesday's return fixture, after it was ruled Santos had fielded an ineligible player.
It was a drama-filled evening after CONMEBOL controversially overturned the result of last week's Copa Libertadores first-leg clash as Independiente advanced to the quarter-finals ahead of Santos.
Santos and Independiente played out a goalless draw on August 21 but the latter were awarded a 3-0 victory just hours before Tuesday's return fixture after the Brazilian side fielded an ineligible player.
Carlos Sanchez was at the centre of the controversy due to a red card he was given during his River Plate stint in 2015, with Independiente arguing the Uruguay international should have been suspended for the opening leg.
CONMEBOL ruled Sanchez did not serve the entirety of the ban handed out three years ago.
The organisation applied a slightly different ruling to a similar case involving River Plate midfielder Bruno Zuculini, but the Argentinian club had checked with the federation in advance in writing, whereas Santos had purportedly only check via the online registration system.
Zuculini received a ban for upcoming fixtures and the previous results were not altered.
Describing the decision as "embarrassing" on the day of the second leg, Santos released a statement, which said: "Faced with this instability in the political scenario experienced by the Brazilian clubs in CONMEBOL, there is a pressing need for a union of all Brazilian sports representatives so that our football will not be grossly harmed.
"We will go to the last instances to defend our right to compete in equality, as well as that, we will not fade away in the incessant search for justice damages already caused."
Bizarrely, Sanchez played on Tuesday as the away leg between Santos and Independiente was abandoned after Santos fans threw fireworks at the Independiente bench and tried to invade the field with just minutes remaining in a 0-0 draw.
Fans and riot police clashed inside and outside the Estádio do Pacaembu, with fans throwing flares, improvised projectiles and smoke bombs onto the pitch and at police.
Tweeting after the match, Santos' official twitter account, seemingly did little to discourage the violence on display from part of its supporter base. It said; "On the field, 0 to 0 in the aggregate. In court, Santos 0, Independiente 3. Thank you for your unconditional support, Santos Nation!"
Independiente, whose Maximiliano Meza missed a penalty in first-half stoppage time, will face either River or Racing Club in the quarter-finals.
Gremio reached the last eight after edging Estudiantes 5-3 on penalties in Porto Alegre, where the tie finished 3-3 on aggregate following the former's 2-1 victory on Tuesday.
Next up for Gremio are Atletico Tucuman, who prevailed 2-1 on aggregate despite a 1-0 loss at Atletico Nacional.