Robert Moreno has been named as the permanent Spain head coach, with Luis Enrique stepping away due to personal reasons.
Former assistant coach Moreno oversaw Spain's past three matches after Luis Enrique was granted leave following a family emergency in March and will remain in charge until the end of Euro 2020.
Moreno and the Royal Spanish Football Federation (RFEF) were keen to see the former Barcelona boss return for the next international break in September.
However, it was confirmed on Wednesday that Moreno will take on the job on a full-time basis in the latest coaching change for La Roja.
"Luis Enrique has informed us that he will not continue as coach. I have to thank him, he has behaved with the RFEF in a '10' manner, we do not have the slightest rebuke. Our doors will always be open to him," said RFEF president Luis Rubiales.
"The decision of the RFEF is to trust Robert Moreno as the coach. He will continue on the same duration of the contract that was already signed. He will be in charge of taking us to Euro 2020 and of doing a good job if we qualify."
Moreno said: "I want to thank you [the RFEF] for placing your trust in us. It's a bittersweet day.
"I didn't expect to be the head coach this way. We are going to try to continue the high-level work that Luis started.
"I've been involved in football for many years, and since I was 14 years old I've thought about reaching the highest level. But I did not expect it this way, and Luis has agreed and supported us."
Spain sacked Julen Lopetegui on the eve of last year's World Cup after he agreed a deal with Real Madrid, before Luis Enrique came in for Fernando Hierro following an underwhelming tournament in Russia.
The three-time European champions finished second behind England in their Nations League group but have since won their opening four Euro 2020 qualifiers.
RFEF sporting director Jose Francisco Molina said the decision to appoint Moreno was made in a bid to maintain continuity.
"Robert Moreno was the only possibility we considered," said Molina.
"A year ago we started a sports project that is going great and we wanted to continue that project. If we signed another coach, the project would have changed."