The character Agnes Browne originated in a radio play broadcast on Irish station RTÉ 2fm in 1992, before appearing in a series of books written by Brendan O'Carroll from the mid-1990s onwards.

The books were adapted into the 1999 film Agnes Browne starring Anjelica Huston, and following its success O'Carroll wrote a series of stories in which he himself played Mrs. Browne (with the spelling later changed to 'Brown' for the sitcom), casting many of his own relatives as other characters.

Seven film-like adaptations were made and released straight to DVD in Ireland as 'Mrs Brown(e)'s Boys – The Original Series', and these were later adapted into seven stage plays performed on tour.

The stage show got its breakthrough outside Ireland at the Pavilion Theatre in Glasgow, where it initially didn't sell well until O'Carroll suggested a 2-for-1 ticket deal, after which it became a hit and the venue became known as 'The Home of Mrs Brown'.

The TV series was developed after BBC Scotland producer Stephen McCrum approached O'Carroll in early 2009, but production of the pilot was delayed by a year due to the Jonathan Ross/Russell Brand scandal; the pilot was filmed in November 2009 and the BBC commissioned a full series within three weeks of viewing it.

The show is deliberately recorded in an informal style, leaving in bloopers such as actors fluffing lines, corpsing, and set or prop malfunctions rather than editing them out, with crew and equipment sometimes visible on camera.

Mrs. Brown's Boys is recorded at BBC Pacific Quay studios in Glasgow in front of a live studio audience, who are shown at the beginning and end of each episode.

English actor Burt Kwouk was asked to play the character Mr Wang for a planned spin-off film, but had to decline due to illness preventing him from travelling to Dublin; O'Carroll said he would take on the role himself if the film were made, and Kwouk died in 2016.

Despite consistently poor reviews from critics who compared it unfavourably to Father Ted, Mrs. Brown's Boys became a huge ratings success, with the 2011 Christmas episode drawing a 48.6% audience share in Ireland and over one million DVD copies of series one sold in Ireland and the UK between October 2011 and February 2012.

Due to copyright issues, several musical performances were cut from the Series 1 DVD release, including Mrs Brown singing Altered Images' 'Happy Birthday', the cast singing The Proclaimers' 'I'm Gonna Be (500 Miles)', and Buster singing the Mission: Impossible theme tune.

In 2022, the show crossed over with Tyler Perry's Madea franchise in the film A Madea Homecoming, with Brendan O'Carroll and Jennifer Gibney reprising their roles as Agnes and Cathy Brown.