Flores takes over the reins from Tshegofatso Mashego, who will now serve as an assistant coach.
Mashego helped the side gain promotion last term from the ABC Motsepe League via the play-offs.
Eagles announced the developments on Twitter, saying: "Super Eagles FC have appointed Spanish-born Antonio Jesus Flores as the new head coach of the team with Tshegofatso Mashego as assistant."
Flores, who has to settle into the new environment and a new league, has previously worked in Uganda at SC Villa and at Sandawana in Lesotho.
He has a big job on his hands at Eagles. The Bethlehem-based outfit are 14th on the log after 10 games, and next host Cape Town All Stars at Goble Park on Sunday.
Flores has to hit the ground running to ensure the team moves away from the relegation zone.