Diego Simeone's side are currently eighth in the table with eight points to show from their four matches, while Betis are one spot and one point above in seventh but have played twice more than the capital club.
Atletico have made an encouraging start to their league season, winning two and drawing two of their four matches, including a 2-0 victory away to Celta Vigo last weekend.
Luis Suarez was again on the scoresheet for Simeone's team in Vigo, but the Madrid giants will enter Saturday's contest off the back of a heavy defeat to Bayern Munich in the Champions League.
Indeed, the European champions recorded a 4-0 victory over Atletico at the Allianz Arena on Wednesday night, which has already put the Spanish club on the back foot in Group A.
The comes are coming thick and fast at the moment, though, and Simeone will be looking for his side to pick up all three points on Saturday ahead of their next European game at home to RB Salzburg next week.
Atletico are actually unbeaten in La Liga since losing at Real Madrid on February 2, but they have drawn three of their last five in Spain's top flight, including a 0-0 with Villarreal in their last home league match.
Betis, meanwhile, have struggled for consistency in the early stages of the season despite showing some positive signs under new head coach Manuel Pellegrini.
The Seville club have won three and lost three of their first six matches of the campaign to occupy seventh spot, although the majority of the teams around them have two or at least one game in hand.
Los Verdiblancos entered the October international break off the back of an impressive 2-0 win at Valencia, but they suffered a 3-0 home defeat to Real Sociedad last weekend.
It is difficult to know what to expect from Betis on a week-to-week basis, but Pellegrini has a talented squad to work with, and it should be an interesting contest in the Spanish capital this weekend.
Atletico have won three of their last four La Liga meetings, while Betis have not been victorious away from home in this fixture since December 2011, which is an indication of the size of their task on Saturday night.
Atletico Madrid La Liga form: WDDW
Atletico Madrid form (all competitions): WDDWL
Real Betis La Liga form: WWLLWL
Pellegrini is expected to shuffle his pack following the disappointing defeat by Sociedad, with Portugal international William Carvalho likely to earn a spot in midfield.
Atletico Madrid possible starting lineup:
Oblak; Trippier, Savic, Hermoso, Lodi; Correa, Torreira, Koke, Lemar; Suarez, Felix
Real Betis possible starting lineup:
Bravo; Ruibal, Bartra, Sidnei, Moreno; Rodriguez, Carvalho; Joaquin, Fekir, Tello; Sanabria
We say: Atletico Madrid 1-0 Real Betis
Atletico ran out 1-0 winners when these two teams locked horns in the corresponding game last season, and we are expecting the same scoreline to occur here. Atletico have only conceded once in the league this term, and Simeone's side should secure another three points to continue their solid start to the La Liga campaign.