Having won the competition in 2006 and 2010, the Brazilians progressed to Group 1 and will play against compatriots Santos, Peru's Juan Aurich and Bolivian giants The Strongest after a 3-2 aggregate win.
In the first minute, Inter defender Nei fouled Guillermo Beltran in the box and the referee blew for a penalty and Jorge Nunez netted from the spot.
However, Mauricio Casierra fouled Oscar in the box and Andres D'Alessandro scored with another penalty at the 11th minute.
Tinga gave Inter the lead after he finished after a D'Alessandro pass in the 22nd minute, three minutes before Mario Gonzalez equalised.
The second half was also exciting but without further goals as Once Caldas failed to get the third goal they needed.
D'Alessandro told Fox Sports: "We took a minor lead in Brazil, but tonight we made it and we were worthy of the progression.
"We played a great first half. We scored two away goals and we knew Once Caldas had to score two goals to qualify. We were surprised in the beginning of the game, but we played like we know and scored by playing good football."
Another Brazilian team to clinch the qualification to the Group Stage is Flamengo, as they saw-off Bolivia's Real Potosi 2-0 in Rio de Janeiro.
A Leo Moura header after a Ronaldinho free-kick put Flamengo ahead and Ronaldinho consolidated the win in second-half stoppage time to celebrate a 3-2 aggregate triumph.
In the second half, Real Potosi defender Claudio Centurion was sent off after a tough tackle on Leo Moura.
Ronaldinho was very happy for the win and told Globo TV: "It was everything I've dreamt. The goal of taking Flamengo to the Group Stage of the Libertadores was achieved."
Emelec of Ecuador, Argentina's Lanus and Paraguayan giants Olimpia will be Flamengo's rivals in Group 2.