Naomi & The Segos traces its origin back to The Harmony Kings, a group founded by brothers James, W.R., and Lamar Sego in the 1950s. The brothers changed their name to the Sego Brothers Quartet shortly thereafter, and secured a show on WMAZ-TV in Macon, Georgia. One day, when a group member fell ill, James Sego asked his wife Naomi to fill in. She did so well that she became an official group member in 1958, and the group name was changed to the Sego Brothers & Naomi.

The group's first album featured the song "Is My Lord Satisfied With Me" and quickly sold over 300,000 copies. In 1962, the group recorded another album, featuring "Sorry, I Never Knew You"; this project sold over a million copies, the first Southern Gospel project to reach that mark. Following the success of the song, the group appeared on the Grand Ole Opry and the Gospel Singing Jubilee.

In 1967, Lamar Sego left the group to tour with his family as the Lamar Sego Family. Health issues forced W.R. Sego off the road in 1979. Not long afterwards, James died during open heart surgery; Naomi decided to carry the group on; she renamed the group Naomi and the Segos in the 1980s.

Naomi Sego remarried in 1983, marrying Vernon Reader, an evangelist from Texas. He passed away in 1998; at that time, the group's lineup consisted of tenor William Pippin and baritone singer Scott Spangler. Pippin left in 2000 and passed away in 2007; Spangler left in 2003, and returned in 2008. Also in 2008, former tenor Jerry Gill, who had been a previous member of the group but left in 1980, rejoined the group. Spangler came off the road again in 2010, and was replaced by eighteen-year-old baritone Ethan Brooks; pianist Bryant Thigpen is also a member of the group.

Naomi Sego Reader was inducted into the Southern Gospel Music Association Hall of Fame in 2001, and her late husband James was inducted in 2007.