Luis Rubiales, president of the Spanish football federation, told reporters Wednesday that Enrique is stepping down for personal reasons and that his assistant, Robert Moreno, will take the reins on a permanent basis.
Enrique led La Roja to five wins in seven matches at the helm.
"It was a decision Luis Enrique took himself, which we are grateful for," Rubiales said, according to the BBC. "We will have a perfect memory of him. It's a personal matter which doesn't depend on us. We think it's the best thing to do."
Moreno has long served as Enrique's right-hand man, working in tandem with the 49-year-old at Roma, Celta Vigo, and Barcelona. Enrique decided to bring Moreno with him when he was named Spain's new head coach in July 2018.
After being hired, Enrique steered Spain through the inaugural UEFA Nations League campaign. However, losses to England and Croatia - the only defeats of his tenure - denied the side the top spot in its group and a place in the Nations League semifinals.
Enrique then left the national team in March while attending to a "family matter of an urgent nature," according to Reuters. Moreno stepped in to lead Spain to wins over Malta, Faroe Islands, and Sweden.
"I want to thank you for the trust you place in us. It's a bittersweet day," Moreno said. "I didn't expect to be the head coach this way. Let's try to carry on the top work that Luis started."
Moreno will now begin preparations for Spain's next Euro 2020 qualifier on Sept. 5 against Romania.