Lucas Torreira, Angel Correa and Mario Hermoso were just three changes from the side that crashed to the ground against Bayern Munich in the UEFA Champions League group stages.
Atletico threatened the breakthrough just after the midway stage through Luis Suarez from outside the area, but the attempt flew wide of goal.
The counterparts pushed for a way in shortly before the halftime interval, but Atletico's stringent all-round play gave the side no room to move.
Suarez had another chance to give Atleti the lead from the edge of the danger area, but send a thumping drive from afar wide of the far post.
Atletico hit the front straight after halftime when Marcos Llorente charged into the danger area to fire past Betis goalkeeper Claudio Bravo from a tight angle.
Hector Herrera and Yannick Carrasco entered in place of Thomas Lemar and Torreira during the interval, as Atleti became the first side to rung the changes.
Betis attempted an immediate equaliser from a looping attempt by William Carvalho, but Atletico goalkeeper Jan Oblak came up with smart reflexes to smother the Portuguese.
Manuel Pellegrini's side were reduced to ten players on 74 minutes when Martin Montoya got his marching orders for bringing down Carrasco with help from the Video Assistant Referee (VAR).
Atletico made sure of the points right at the death when Suarez finally made his presence felt with an easy tap-in to help his side to second in LaLiga.