Macdonald attended Bishopbriggs High School. She is a self-taught musician, playing her father's guitar after being inspired by Travis at the T in the Park Festival in 2000, where she heard Travis' song "Turn" and wanted to play it herself.

Macdonald started playing in pubs and coffee houses around Glasgow at 15, including the Brunswick Cellars on Sauchiehall Street. She sent a demo CD in response to an advertisement placed in the 'NME'

In an interview with Hit Quarters, Wilkinson said he was "literally aghast" at her songwriting abilities when first he heard Macdonald play the songs 'This is the Life' and 'Mr Rock n Roll'.

" I said, "Amy, who wrote those songs?" And she said, "I did." I said, "No, you didn't," giggling, hoping she really did. She said, "I bloody well did!" I told her she was extraordinarily talented, and the moment she sang those songs I remembered her voice and the hooks, which out of 500 demos submitted was a very good sign."

Wilkinson then spent around eight or nine months recording demos with Amy at his home studio with a view to securing a record deal for his new client.Reviewers have described Macdonald as softly spoken but with a booming singing voice. Despite her Scottish origins, her singing voice is described as partly Irish and similar to Dolores O'Riordan of The Cranberries.

Macdonald got press coverage when she questioned whether the 2007 winner of 'The X Factor', Leon Jackson, was suffering from tonsillitis, referring to it as "lazyitis". This was because Amy had tonsillitis at the same time but still performed at Glasgow and at the BBC's 'Hogmanay Live' show the same night.

Macdonald is the first artist to have a single featured on Bebo/ i Tunes' "Free Single of the Week" program. The free single, "Youth of Today", was written when she was 15.

She appeared as a musical performing guest on British and foreign shows including 'The Album Chart Show', 'Loose Women', 'Friday Night Project', 'Taratata' (France), and 'This Morning'. She won the best newcomer award at the Silver Clef awards.

In 2007, Macdonald released her debut album, titled 'This Is the Life'. The album became the UK's #1 album for 1 week. The album debuted at #2 in the UK in its first week but then fell to 4 and then to 6 in its third week. The first single from the album, "Poison Prince", was only a limited release. The second single, "Mr. Rock and Roll", became Macdonald's first top 40 song charting at #12 in the United Kingdom. However the third single, L.A., missed the top 40 at #48, but however managed #5 in the Scottish singles chart. The fourth and most successful single, "This Is the Life", charted at #28 in the UK, but was #1 in five other European countries. The single was awarded Platinum in Germany and Belgium and Gold in Spain and Switzerland. The fifth single, "Run", gave Macdonald her second lowest chart position in the UK at #75. However Run charted at #36 in Germany. The sixth and final single was the re-release of "Poison Prince", but charted at #148 in the UK, Macdonald's lowest chart position.

The album has sold over 3 million records worldwide.

Macdonald stated that she started working on her second album in 2009. According to her Twitter she was writing for the album and she had recorded some bedroom demos. She said " Some of the sounds are just amazing and we've managed to persuade one of my favourite artists to whack some stuff down on them, but you'll have to wait and see."

According to music-week magazine the album will be released on 8th March 2010.

It will be preceded by the single, "Don't Tell Me That It's Over" a week earlier on 1st March 2010. The single was released to UK radio on 11th January. Amy performed the new single on the Simon Mayo Show on BBC radio 2 on the same day.

"Don't Tell Me That It's Over" has been released to radio in countries like UK, Switzerland, Germany and France. To promote the album, she was in concert in Paris at La Cigale February 3, 2010.

-In December 2008 Macdonald was voted "Scottish person of the year" by the 'Daily Record'.
-Macdonald was set to perform, along with U2, at the German Echo awards, where she was nominated in the category "Best International Female".
-Amy Macdonald won the "Best International Newcomer" Award, and played "This Is the Life" at the award show.
-She won Best Newcomer at the Tartan Clef Awards.
-Macdonald won Best Newcomer at the Silver Clef Awards
-Macdonald won Best International Album and Best International Song at the Swiss Music Awards.