Cleiton Xavier and Keirrison scored in each half as the Brazilians shrugged off the difficulties of playing at one of the world's highest first division grounds to complete a 7-1 aggregate win over the Bolivians in the preliminary round tie.
As the former silver mining town of Potosi does not have a commercial airport, Palmeiras flew into Sucre and then had to travel three hours over mountain roads to reach the stadium for Wednesday night's game.
The club hired 10 four-wheel drive vehicles rather than a conventional bus to transport the players to reduce the journey time and arrived only two hours before kick off.
Palmeiras will face defending champions LDU of Ecuador, Chilean champions Colo Colo and compatriots Sport Recife in their group.
Former Brazil and Real Madrid coach Luxemburgo has won the Brazilian championship five times with four different clubs but the Libertadores, the region's equivalent of the Champions League, has so far eluded him.
Universidad de Chile and Estudiantes also progressed on Wednesday, both winning their ties on away goals.
Universidad de Chile lost 2-1 away to Mexico's Pachuca, playing for 80 minutes with 10 men after Mauricio Arias was sent off for punching an opponent early on.
Gerardo Rodriguez put Pachuca ahead with a 25th-minute penalty but Marco Estrada grabbed the crucial away goal when he scored from a free kick in the 59th minute.
Damian Alvarez's 86th minute goal was too late for Pachuca as the tie finished 2-2 on aggregate. The Beavers' frustration boiled over when Alvarez was sent off in injury-time for a lunging tackle.
Substitute Ramon Lentini's 76th-minute goal gave Argentina's Estudiantes a 1-0 win at home to Sporting Cristal and a 2-2 aggregate draw which was enough to send them through.
