Mary Lou Lord first gained notice playing acoustic guitar and singing in and around Boston's subway stations (particularly on the Red Line, as noted by the name she chose for her music and lyric publishing company, On the Red Line Music, administered by BMI.)

She allegedly dated Nirvana frontman Kurt Cobain (prior to Courtney Love) before the group was signed to Geffen Records. Lord also toured three separate times with Elliott Smith during the 1990s. Her recordings have been a mixture of covers (including songs by Elliott Smith and Richard Thompson) and original material, with a number of songs written by, or in collaboration with, Nick Salomon of the British band the Bevis Frond including the track "Farming it Out" which appears on Shut Eye's Buzzlighter #8: Natural Anthems.

Her recording of Daniel Johnston's "Speeding Motorcycle" (which originally featured on her self-titled 8-song Kill Rock Stars release) was featured in commercials for Target stores, after which her label reissued the song as the lead-off track of a CD single which also included two demo recordings from the sessions for Got No Shadow.

Her major label debut Got No Shadow was released in January of 1998 by Sony Records to lukewarm reviews, and poor sales. Sony quickly dropped Lord from its roster. As of 2006, Lord still owes Sony Music the production expenses from this commercial failure, which many complained was over-produced, and the wrong showcase for Lord's unique vocal stylings and performing strengths. The only song that managed (light) airplay was "Lights Are Changing".

A far better showcase of Mary Lou's talents was the 2001 release Live City Sounds. This was a self-released disc of Mary Lou busking in the Boston subway, and found her more in her element. The disc was later re-released after Mary Lou signed to Rubric Records.

She announced in 2005 that she suffered from a rare vocal chord affliction known as spasmodic dysphonia. She thereafter became more involved in A&R work and started a new management company with her husband Kevin Patey.