O'Donnell was born in the early 1980s and grew up in Motherwell with two older sisters. She initially studied international law at university but dropped out after three months to take up acting.

Early in her acting career O'Donnell mainly worked in theatre, featuring in productions of Boys, The Hard Man, Eigengrau, and Yerma.[2] She had small roles in BBC television productions Feel the Force (2006) and Holby City (2012). She played a lead role in My Romantic History, a play at the Edinburgh Fringe which won the 2011 Fringe First award.

From 2014 to present she has appeared in the recurring role of Alison McIntosh, in the Scottish television crime drama, Shetland made by ITV Studios for the BBC.

In 2017 she was part of the cast of the BBC Radio 4 play Synonymous, written by D C Jackson.

O'Donnell's partner is Scottish playwright D C Jackson, they have a daughter together, born in late 2017 and a son, born in late 2020. They met while O'Donnell played the lead role in Jackson's play My Romantic History at the Traverse in Edinburgh, but only became a couple later.