The roots of the band were planted in 2003 when Ryan Lenssen and Adrian Jewett formed Thee Oneironauts (O-nye-rawn-nauts).

The pair recorded and self-released an EP entitled Night of the Lawnchairs on the GROK Studios imprint, which had also released Lenssen's concept band "Rushing To Redlights".

TMSR spent much of 2007 prepping their second album, Population, which was released by Arts & Crafts on October 2, 2007, to generally positive reviews.

In an interview from June 17, 2008, guitarist Nick Greaves stated that the band will be recording their third album with Broken Social Scene and Super Furry Animals producer David Newfeld, and hinted there might be a slight change of musical direction.

[4] On August 14, their song "Humble Peasants" was featured in the trailer for A Generation After Genocide, a documentary about the healing power of soccer in Rwanda.

The Most Serene Republic have announced a return to action with their first new album in six years, Mediac, which was released on November 13, 2015, on MapleMusic Recordings.