Kirkbride was noticed by casting directors for the British soap opera Coronation Street when she acted in a Jack Rosenthal play, Another Sunday and Sweet F.A. (1972), for Granada Television. She played the bit part of Deirdre Hunt in Coronation Street from November 1972. The character’s role grew and after further appearances in 1973, Kirkbride signed a contract with the serial in 1974. From then on, the character of Deirdre Barlow became infamous for her very large spectacles and her husky voice (a result of Kirkbride’s own chain smoking).

She married former actor David Beckett in 1992. They met on the set of Coronation Street, when Beckett joined the cast as her character Deirdre’s boyfriend.

In 1993, Kirkbride was diagnosed with Non-Hodgkin’s lymphoma. She spoke to the British press about her bout of depression following the diagnosis. She was cured within a year of being diagnosed.

In 1998, Kirkbride ran away on This Is Your Life. In 2012, Kirkbride completed a documentary entitled Deirdre & Me, a 60-minute special to celebrate her 40th year of playing Deirdre. She also completed a documentary in 2001 also entitled Deirdre & Me. Her late father Jack Kirkbride also gave an interview in the documentary in 2001.

In 2007, Kirkbride starred in the first episode of You Don’t Know You’re Born, a genealogy documentary on ITV1. It was revealed she had Irish ancestry in Gort, County Galway.

On 29 September 2014, it was announced Kirkbride would have a three-month break from the show and prior to her death, she had filmed no official last scenes, making her final scenes the ones aired on 8 October 2014 with her character’s absence in the soap being explained as staying with a friend until July 2015, when her character Deirdre was killed off with Bev Unwin (Susie Blake) returning to tell Ken and Tracy that she died on the day of her 60th birthday party and homecoming. At the 2015 British Soap Awards, she posthumously received the Outstanding Achievement award, which was accepted by her husband.

Kirkbride died of breast cancer in a Manchester hospital on 19 January 2015, aged 60. Her funeral was held on 27 January 2015 in a private ceremony. William Roache, Beverley Callard, Kate Ford and former co-star Johnny Briggs were in attendance.

A public memorial service for Kirkbride was held at Manchester Cathedral on 30 May 2015.