The song was released on July 9, 2020, through Universal Music Latino, as the second single from her third studio album, KG0516.

And when we went out, in the middle of dancing, and whether I'd go home with him or not.Billboard stated "It’s her own, very personal, and feminine, take on reggaeton; a Karol G stamp that makes her stand out in the genre.

The song received a Latin diamond certification by the Recording Industry Association of America (RIAA) on April 1, 2021, for sales of 600,000 equivalent-units.

The music video for "Ay, Dios Mío" was directed by Mike Ho and was released on Karol G's YouTube channel on July 9, 2020.

In collaboration with Billboard and energy drink Rockstar, Karol G performed "Ay, Dios Mío!"