A double from Brazilian forward Diego Costa overshadowed David Villa's debut for Atleti after Spain's all-time record goalscorer joined from Barça for a paltry initial fee of just €2.1 million ($2.8 million, £1.8 million) last month.
However, Costa believes Villa will prove to be a more than capable deputy for Falcao who scored 70 goals in his two seasons with Los Rojiblancos before a 60 million euro move to Monaco in June.
"You notice the absence of Falcao because he is a great player, but we have Villa who is also a beast and we know that he is going to do just as well," Costa told the club's website.
"His work and commitment for the team is amazing. He is a very humble person and he has a great attitude. I think with the quality he has he will give a lot to Atletico."
Villa will be desperate to impress against his former employers after never truly getting a consistent run in the side after breaking his tibia in the Club World Cup back in December 2011.
A troublesome on field relationship with Lionel Messi and Barca's capture of Neymar in June made Villa's exit from the Camp Nou somewhat inevitable.
But with Champions League football and a regular starting place on offer at Atleti he has the perfect platform to show he should be Vicente Del Bosque's first-choice striking option come the World Cup next year.
Under Diego Simeone's tutelage Atleti have already improved mightily and an unlikely success against the Catalans over two legs would mean a fourth trophy in little over a year.
Simeone ruled out any idea of a title challenge from Atleti in the strongest terms following the Sevilla result, castigating La Liga as a "boring" championship that is only about two clubs.
However, Barca goalkeeper Victor Valdes rejected claims that there is no competition for the big two in Spain and is expecting a tought test from Atleti.
"They showed against Sevilla that they will be a very difficult opponent. It will be another test for this Barca.
"You only have to watch how Betis played against Real Madrid, the Sevilla-Atletico game and Valencia this weekend. It will be a difficult game wherever we play."
After a dream start to his career in charge of the Spanish champions thanks to Sunday's 7-0 trouncing of Levante, Barca boss Gerardo Martino could hand Neymar his first competitive start at the Vicente Calderon.
The Brazilian only made an appearance as a second-half substitute at the weekend.
And while the goalscoring performances of Pedro and Alexis Sanchez may keep him on the bench once more, Spanish international duo Andres Iniesta and Jordi Alba are expected to return after also being rested by Martino following their gruelling trip to Ecuador to represent the world champions last week.