The Isaacs trace their roots back to the 1970 marriage of a banjo player from Kentucky and a Jewish folk singer, daughter of Polish Holocaust survivors, who had never heard a bluegrass song. Shortly afterward, Joe and Lily Isaacs attended a church service after Joe's brother passed away; this moved them to become active Christians. They began singing in church together, and Joe formed the Calvary Mountain Boys, a group that traveled to area churches. 

In 1975, Joe formed Joe Isaacs and the Sacred Bluegrass. The Isaacs children - Ben, Sonya, and Becky - started learning harmonies and picking out instruments, making guest appearances with the group. Sonya learned to play mandolin when the group's previous mandolin player left. But by 1985, the challenges of keeping a group on the road led Joe to the point of quitting. Ben, Sonya, and Rebecca approached him about transitioning to becoming a family band, and the Isaacs hit the road in 1986.

A turning point came in 1992 and 1993, when the Isaacs moved from in-house booking to a booking agent and signed with Horizon Records. From an Opry appearance to their first #1, the group received the first of many honors and accolades. After several years of Gaither Homecoming video appearances and periodic concert series appearances, they joined the tour full-time in 2003.

All three Isaacs children are active songwriters; they have penned many of the Isaacs' hit songs, and songs for many other artists, including Gold City, Jeff and Sheri Easter, Mike and Kelly Bowling, Mark Lowry, Vince Gill, Trisha Yearwood, and Cherryholmes. Members of the Isaacs have made numerous guest appearances on other artists' records, singing with everyone from Dolly Parton to Vince Gill to Mark Lowry. Ben Isaacs has produced and played for numerous artist projects, including projects by Merle Haggard, George Jones, and Cherryholmes, and for a Jimmy Martin tribute project. He has received five Grammy nominations for his Martin and Cherryholmes work.