Benedetti was born in West Kilbride, North Ayrshire, to an Italian father and a Scottish mother. She started learning to play the violin at the age of four. At age eight, she became the leader of the National Children's Orchestra of Great Britain. By the age of nine, she had already passed the eight grades of musical examinations while attending the independent Wellington School, Ayr, and in September 1997 began to study at the Yehudi Menuhin School for young musicians under Lord Menuhin and Natasha Boyarskaya in rural Surrey, England.
At the end of her first year (1998), she played solo in the school's annual concert at Wigmore Hall, and performed in London and Paris as a soloist in Bach's Double Violin Concerto (together with Alina Ibragimova). She played in a memorial concert at Westminster Abbey celebrating the life and work of Yehudi Menuhin.
In 1999, Benedetti performed for the anniversary celebrations at Holyrood Palace with the National Youth Orchestra of Scotland in the presence of HRH The Prince Edward.
In 2000, Benedetti performed with the Royal Scottish National Orchestra and the Scottish Opera.
She played to the Prince again in 2001 when she performed a concerto with the London Mozart Players at St. James's Palace. Subsequent performances followed with the City of London Sinfonia, as well as the Royal Philharmonic Orchestra, Scottish Opera, Scottish Chamber Orchestra, Royal Scottish National Orchestra, etc.
In August 2002, she won the UK's Brilliant Prodigy Competition, broadcast by Carlton Television. She left the Menuhin School shortly after, and at the age of 15 began studying privately with Maciej Rakowski, former leader of the English Chamber Orchestra.
Benedetti received an honorary doctorate from Heriot-Watt University in 2010 In September 2012, she played at the Last Night of the Proms. In the New Year Honours 2013 Benedetti was appointed as a Member of the Order of the British Empire for services to music and charity.
In spring 2003, Benedetti, invited as a soloist by the London Symphony Orchestra, participated in the recording of the DVD titled "Barbie of Swan Lake" at Abbey Road Studios. In October 2003, as the extra feature on this DVD, "Playing With Passion" was filmed and released by Mattel. BBC Scotland, using this DVD, created a documentary on Benedetti, which was broadcast on television in the U.K. in March 2004.
At the age of 16, she won the BBC Young Musician of the Year competition in May 2004, performing Karol Szymanowski's First Violin Concerto in the final at the Usher Hall in Edinburgh, with the BBC Scottish Symphony Orchestra. Because of this victory, she won the music section of the Top Scot award in December 2005.
At the end of 2004, she agreed to a £1m six album recording contract with Deutsche Grammophon/Universal Music Group Classics and Jazz.
Aside from solo performances, Benedetti performs in a trio with the German cellist Leonard Elschenbroich, and Russian pianist Alexei Grynyuk.
In November 2007, Benedetti was awarded an honorary doctorate by Glasgow Caledonian University. She is one of the youngest recipients of such an award. In November 2011, Benedetti received an honorary degree from the University of Edinburgh.
Benedetti was elected an honorary fellow of the Royal Society of Edinburgh in March 2017.
In May 2017, she was presented with the Queen's Medal for Music, the youngest of the twelve people to receive the award since it was established in 2005.