That same year, still living in St. Catharines, he collaborated on recording and releasing a cassette, Out of the Duff, with a singer-songwriter friend named Claudio.

They became friends, and Wiseman agreed to produce and arrange Sexsmith's next release in between his tours with the band Blue Rodeo.

After the album Grand Opera Lane was rejected by several Canadian labels, the pair released it independently in 1991.

Grand Opera Lane was credited to "Ron Sexsmith and the Uncool"; the backing band including Don Kerr and Steve Charles, and also featured Sarah McElcheran (horn arrangements) and Kim Ratcliffe on electric guitar.

Attention garnered by the song "Speaking with the Angel", Sexsmith earned a contract that led to his self-titled album in 1995.

[9] On May 1, 2001, Sexsmith performed "Just My Heart Talkin'" on the BBC's Later... with Jools Holland musical showcase, alongside R.E.M., Orbital, India.Arie, and Clearlake.

[citation needed] In 2002, Sexsmith recorded a cover version of "This Is Where I Belong", the title track for a tribute album called This Is Where I Belong – The Songs of Ray Davies and the Kinks, which included contributions from Damon Albarn, Bebel Gilberto, and Queens of the Stone Age, among others.

On June 16, 2011, Sexsmith and his band performed The Kinks' song "Misfits" with Ray Davies at the Meltdown Festival in London, England.

It was well received and Publishers Weekly wrote that the "novel has much the same effect as his music, conveying uncertainty with fearlessness and heart.

In 2002, he sang a duet with Coldplay's Chris Martin in the song "Gold in Them Hills", which appeared as a bonus track on the album Cobblestone Runway.

In 2005, he released a collection of songs recorded with drummer Don Kerr during the production of Retriever, called Destination Unknown.

Sexsmith's songs have been performed and recorded by a number of well-known musicians, including Elvis Costello, Feist, Rod Stewart, and Emmylou Harris[15] His song "Secret Heart" has been covered by Rod Stewart, Feist, and Nick Lowe.