The couple made the bombshell announcement Wednesday, after filing papers in Tennessee citing irreconcilable differences.
"As you can imagine, this is a very difficult time for our family," the pair said in a statement. "We are trying to work through some personal matters. We appreciate your thoughts and prayers."
The couple wed in December of 1992.
They had three children together -- daughters Miley, 17, and Noah, 10, and a son Braison. Tish had two children, Brandi and Trace, from a previous marriage. The 49-year-old country singer adopted both when they were young children.
Miley began her career with a starring role in the Disney TV show "Hannah Montana" which also featured her dad. She has since gone on to pursue an acting and singing career -- her third album "Can't Be Tamed" was released in June.
Cyrus has taken heat for what critics have said is an ongoing effort to shed her good-girl status by flaunting her sexuality in the music videos for the album.
"It is unfortunate that she would participate in such a sexualized video like this one (the video for 'Who Owns My Heart'),” Tim Winter, President of the Parents Television Council (PTC), told TMZ on October 9.
The video shows the Disney darling -- who turns 18 in November -- waking up blindfolded and writhing around on a bed in her underwear before she moves on to a sexy dance party where she can be seen grinding up against various partners.
Billy Ray Cyrus is a member of the advisory board for the PTC -- a parent's advocacy group that reviews content based on its potential harm to children.
-NewsCore contributed to this report.