Atleti started the match brightly with Giuliano Simeone having his third minute attempt saved by Barcelona goalkeeper Juan Garcia's outstretched leg.
Three minutes later, a seemingly harmless back pass from Eric Garcia slipped under the Juan Garcia's foot and went over the goal line to hand Atletico the opener.
The home side then doubled their lead in the 14th minute through Antoine Griezmann who finished neatly in the box from a Nahuel Molina pass.
Barca almost pulled one back five minutes later when Pedri hit the woodwork after Los Colchoneros failed to deal with a corner kick before Ademola Lookman (33') extended the lead with a cool finish from a swift move.
The best chance of the half for the Catalans fell to Pedri (39') who was put through by a Jules Kounde pass only for Jan Oblak to close down the angle to make a save for a corner.
However, Atletico were not done for the half with Julian Alvarez rifling the fourth goal home after being set up by Lookman in the second minute of additional time.
The visitors showed more intent in the second half but had a Pedri goal ruled out for offside following a VAR check in the 52nd minute.
Barca failed to trouble Oblak in goals with most attempts not finding the target before things got worse with Eric Garcia (84') being sent off for a reckless challenge on Alex Baena.
Neither side could find the net after the dismissal despite numerous half chances as Diego Simeone's team claimed an emphatic first leg victory at home.
"We found incredible energy in the stadium, life is energy, and we were able to ride that wave of energy," said Simeone after the match.
"The interpretation of the match was very good, with the four forwards interpreting the space very well. Other days we say we lack cutting edge, but today will be remembered for how we played, the players represented it in the best possible way."
Meanwhile Barcelona coach Hansi Flick remains optimistic of achieving a positive result in the second leg at the Spotify Nou Camp in three weeks.
"We are capable of coming back. We will fight and for that reason we need our fans at Spotify Camp Nou," said the German mentor.
“I am proud of my team. It's clear I am not happy with the first 45 minutes, but I am proud of the season we are putting in. We will pick ourselves up and come back. We have a chance of turning it around. We can win each half 2-0.”
The two teams will meet for the second leg on March 3.