Atletico are 15th in La Liga with only one win from their first seven games and are rooted to the foot of Champions League Group D without a win or a goal after being hammered 4-0 at Chelsea on Wednesday.
"I'm here to tell you Atletico and Abel Resino have agreed that we end our relationship," Atletico sports director Jesus Garcia Pitarch told a news conference.
Assistant coach Santi Denia would take charge of Saturday's game at home to fifth-placed Real Mallorca, Garcia Pitarch added.
"I remain convinced that a couple of good results will change all of this," Resino told the same news conference.
The former Atletico goalkeeper stepped in to replace Javier Aguirre at the beginning of February as the side suffered a dip in form last season.
He was unable to prevent them going out of the Champions League to Porto in the first knockout round, but engineered a late surge to grab fourth place in the league and a slot in the Champions League play-off round.
Although they saw off Panathinaikos 5-2 to make the group stages in August, the team have struggled since then and with 17 La Liga goals conceded have the worst defensive record in the top flight.
Spanish media reported Michael Laudrup had rejected an approach to take the helm, and that Quique Sanchez Flores and Luciano Spalletti were among the candidates being considered for the post.
