In 1961, aged fourteen, she had a UK No. 3 hit with her first single, "Don't Treat Me Like a Child" and two number one hits in the UK, "You Don't Know" and "Walkin' Back to Happiness". The latter did not top the UK chart until 19 October 1961, by which time Shapiro had reached 15, on 26 September. She had a No. 2 in 1962 with "Tell Me What He Said", achieving her first four single releases in the top three of the UK Singles Chart. Most of her recording sessions were at EMI's studios at Abbey Road in north west London. Her mature voice made her an overnight sensation, as well as the youngest female chart topper in the UK.
Shapiro's final UK Top Ten hit single was with the ballad "Little Miss Lonely", which peaked at No. 8 for two weeks in 1962. Shapiro's recording manager at the time was Norrie Paramor.
Before she was sixteen years old, Shapiro had been voted Britain's "Top Female Singer". The Beatles' first national tour of Britain, in the late winter/early spring of 1963, was as her supporting act. During the course of the tour, the Beatles had their first hit single and John Lennon and Paul McCartney wrote the song "Misery" for her, but Shapiro did not record the composition. In 1995, during a This is Your Life highlighting her life and career, Shapiro revealed, "It was actually turned down on my behalf before I ever heard it, actually. I never got to hear it or give an opinion. It's a shame, really." Shapiro lip-synched her then-current single, "Look Who It Is", with three of The Beatles (John Lennon, Ringo Starr and George Harrison) on the British television programme Ready Steady Go!.
By the time she was in her late teens, her career as a pop singer was on the wane. With the new wave of beat music and newer female singers such as Dusty Springfield, Cilla Black, Sandie Shaw and Lulu, Shapiro appeared old-fashioned and emblematic of the bee-hived, pre-Beatles, 50s era. As her pop career declined, Shapiro turned to cabaret appearances, touring the workingmen's clubs of the North East of England. Her final cabaret show took place at Peterlee's Senate Club on 6 May 1972, where she announced she was giving up touring as she was "travel-weary" and had had enough of "living out of a suitcase". Later, after a change of mind, she branched out as a performer in stage musicals, jazz (being her first love musically), and more recently gospel music. She played the role of Nancy in Lionel Bart's musical, Oliver! in London's West End and appeared in a British television soap opera, Albion Market, where she played one of the main characters until it was taken off air in August 1986. Between 1984 and 2001, she toured extensively with legendary British jazz trumpeter Humphrey Lyttelton and his band, whilst still performing her own jazz and pop concerts. Her one woman show "Simply Shapiro" ran from 1999 to the end of 2002, when she finally bade farewell to show business in order to concentrate on her Gospel Outreach evenings.
Her autobiography, published in 1993, was entitled Walking Back to Happiness. She appeared as a guest on BBC Radio 4's 'The Reunion' in August 2012. In March 2013 she appeared on BBC Radio 3's 'Good Morning Sunday' and recounted her life growing up as a Jew in the 1950s in London, her musical career and her belief in Jesus as Messiah since 1987. In 1989 Shapiro performed the first of many Gospel Evenings at which she sings a selection of worship songs followed by her telling of her faith in Yeshua, Jesus.
In November 2013 she made her first appearance as part of the Messianic Gospel group "Hebron" alongside Simon Elman and Chrissy Rodgers. The event was held at Hamworthy Social Club in Wimborne, Dorset.