Argentina winger Maxi Rodriguez opened the scoring for the hosts with a header after an hour and striker Ignacio Scocco added a second with a brilliant free kick 10 minutes from time, his sixth goal of the competition.
Striker Jo, fresh from helping Brazil win the Confederations Cup, was denied an equaliser for offside when Atletico trailed 1-0 while Ronaldinho had a quiet night.
The team that comes out on top in Belo Horizonte next Wednesday will meet the winners of the other tie between Paraguay's Olimpia and Independiente Santa Fe of Colombia. Olimpia lead 2-0 after Tuesday's first leg in Asuncion.
"It's a very good result but the tie is open. We've played against the best team in the Libertadores, according to the statistics, and we won with authority," Newell's coach Gerardo Martino said.
Atletico, seeking their first South American club title, are top scorers in the competition with 25 goals in 11 matches and had found the net in every match bar one.
The Brazilian side's goalkeeper Victor made two good saves from man of the match Rodriguez in the first half and the winger also hit the post in an inspirational performance as Newell's look to reach their third final and win the trophy for the first time.