Ernesto Valverde's side have won all seven of their fixtures in La Liga this term and sit six points clear of the Rojiblancos ahead of this weekend's meeting in the capital.
That will be the first for the Blaugrana at the Wanda Metropolitano after the stadium was inaugurated last month, and an eighth win would leave the Catalans in a commanding position at the top of the table.
Here, Goal looks at everything you need to know ahead of the big match on Saturday night...
Ousmane Dembele underwent an operation on a thigh injury he picked up at Getafe last month and the France forward is now expected to be sidelined for up to four months, meaning he will almost certainly not feature again in 2017.
Rafinha and Arda Turan are also out and will play no part in the game against Atletico.
With no players sent off this season and only a handful booked (Gerard Pique and Jordi Alba three times each in La Liga), Barcelona have no suspended stars for the match against Atletico.
BARCELONA POTENTIAL STARTING LINE-UP
With Ousmane Dembele still sidelined, Barcelona boss Ernesto Valverde must decide which player will start in attack alongside Lionel Messi and Luis Suarez on Saturday.
The two South American forwards should feature from the outset, despite turning out for their national teams in CONMEBOL World Cup qualification games over the past week.
Valverde could choose Sergi Roberto on the right, with Denis Suarez and Aleix Vidal also options. Gerard Deulofeu looks unlikely to be included, however, after falling out of favour in recent weeks.
Elsewhere, Andres Iniesta (who recently signed a new "lifetime" contract with the Catalan club), should start in midfield despite a knock.
ATLETICO TEAM NEWS
Atletico Madrid have made a strong start to La Liga and are in fourth place ahead of the game against league leaders Barcelona.
Diego Simeone's side have picked up four wins and three draws in the Primera Division so far and have won both of their home matches (against Malaga and Sevilla) at the recently inaugurated Wanda Metropolitano stadium.
Diego Costa has returned to Atletico from Chelsea, but the Spain striker is uneligible until January due to the club's transfer ban. Meanwhile, right-back Sime Vrsaljko is a doubt for Saturday's game.
BEST OPTA MATCH FACTS
Atletico have not won in their last 14 Liga games against Barcelona (losing eight of those), their worst run without a win against them in the competition.
The Rojiblancos' last win over Barcelona in La Liga was in February 2010, a 2-1 success that was the only defeat for the Catalans in that Primera Division campaign.
Only against Sevilla (23) has Lionel Messi scored more goals in La Liga than against Atletico (22).
Antoine Griezmann has scored in all three of the competitive games which have been played at the Wanda Metropolitano: two in La Liga and one in the Champions League.
Diego Simeone has just won two of his 21 games as coach against Barcelona in all competitions (drawn seven, lost 12), none of them in La Liga.
TV COVERAGE & KICK-OFF TIME
Atletico versus Barcelona kicks off at 20:45 local time at the Wanda Metropolitano on Saturday and will be broadcast live from 19:40 UK time on Sky Sports Football.