After Barcelona dropped points against Levante on Tuesday, Atletico could be within one victory of claiming their second league crown of Simeone's tenure following Wednesday's 2-1 win over Sociedad.
Yannick Carrasco and Angel Correa struck in the space of 12 first-half minutes to give Atletico a 2-0 lead inside half an hour in the Spanish capital midweek.
Carrasco has been involved in 14 LaLiga goals this season (six goals and eight assists), equalling his record in a same campaign in the competition (14 in 2016-17 – 10 goals, four assists).
La Real set up a grandstand finish through Igor Zubeldia but Atletico held on to move four points clear atop the table with two rounds remaining, though city rivals Real Madrid could move back within two by beating Granada on Thursday.
"We knew that we had to win," Atletico head coach Simeone told reporters. "We were ahead in the game against a team that were doing things well, especially away from home.
"The first half was pretty good, we took a 2-0 lead, we had enough chances to have a bigger advantage. Up until the 25th minute of the second half the game was open and at the end of the season winning is very important and then their goal happened as did those last few minutes.
"We were left with the feeling that we suffered in those last few minutes because of Sociedad's desire to try and get a draw."
This is the third time in history Atleti have reached 80 or more points after 36 games played in LaLiga (assuming three points per victory) after 2013-14 (88) and 2015-16 (85).
Atletico are unbeaten in their last 19 matches played on a Wednesday in LaLiga (W15 D4) since a defeat to Madrid in April 2012 (1-4).
"We need to rest. Clearly we're all in a season that has been very tough and that will end up being very tough indeed because of everything that has happened to us as a society," added Simeone. "We started too fast and you all know that and all teams have had to fight against that. We're no exception.
"We have two games ahead and we'll face them in the same way we have the others, game after game, knowing that on Sunday it will be a very important match for us, knowing it will be a very important game for what's to come in LaLiga."
Koke made his 500th appearance for Atleti in all competitions, becoming the second player to reach this figure in the history of the club after Adelardo Rodriguez (550).
"We have two games left, that's a whole world," Koke said. "The league is really tight these last five games, we've always said it. Everyone is dropping points, these games are finals for us, we won this one and on Sunday and we have another final we want to win.
"We're Atleti, if we weren't suffering, it wouldn't be us. Thanks to the fans who came here outside [the stadium] and those who can't. You need your fans to make that extra effort as we did in the last 10 minutes, we could hear them outside. We're grateful."