The only adopted member of her family, Mealing was the youngest of four children, with two sisters and an elder brother. She grew up in Dulwich, South London, with her adoption never being a secret. Although very much part of a strong and loving family, she was always aware that she looked nothing like her siblings and was left feeling that she did not quite fit in. Despite a yearning to know more about her biological parents, Mealing was concerned that looking for them would upset her family.
When she was 15 years old, Mealing's brother died after using heroin. Although Stephen was 14 years her senior, they were very close and it affected her deeply. Realising that "life can be short... there's no point sitting around", she was influenced to "do stuff".
Originally known as Mandy Mealing, her first professional performance was in a Julie Andrews special on BBC television at the age of six. She then started Saturday classes at the Italia Conti Academy, before enrolling full-time at the age of nine. Parts in Just William, The Morecambe & Wise Show and Premiere followed, before she was cast as comprehensive-school pupil Tracy Edwards in Phil Redmond's long-running BBC One children's drama series Grange Hill.
Mealing appeared in The Darling Buds of May, Four Weddings and a Funeral, In Deep, Capital City, The Bill, Midsomer Murders, and Delise in the 1990 mini series The Gravy Train. She appeared in the TV miniseries, Jake's Progress, as Robert Lindsay's errm bit on the side, in 1995. She played Ruth Manning in the first series of Russell T Davies' 1920s period drama series The Grand in 1997, and JoJo in Jimmy McGovern's The Lakes in 1999. Alan Bleasdale wrote the part of Katie in "Jake's Progress" for Amanda after working with her on GBH.
Mealing appeared as cardiothoracic consultant Connie Beauchamp in BBC One's BAFTA award winning medical drama series Holby City from 1 June 2004 to 28 December 2010, announcing her decision to quit Holby City in October 2010, filming her final scenes in October and her departure seeing her resigning from her position at the hospital.
On 16 July 2010, Mealing appeared on ITV's The Five O'Clock Show with Jason Donovan and Corrine Bailey Rae. In 2011, Mealing appeared in the Sky1 series Strike Back: Project Dawn as Colonel Eleanor Grant. In 2013, Mealing appeared in an episode of the BBC series Death in Paradise. Mealing also appeared in the latest series of ITV's Law and Order: UK playing a solicitor.
On 29 March 2014, Mealing reprised her role as Connie Beauchamp, but in Holby City's sister show Casualty, in which her character quickly rose to the role of emergency department deputy clinical lead and later clinical lead. Her return was well received, though the Daily Mail called her out as being unrealistic of the modern NHS, describing her as "impossibly glamorous", "wearing more make-up than the entire cast of TOWIE" and "teetering around saving lives in her tight pencil skirts and towering heels".
On 26 February 2016 when on an interview on This Morning, Ben and Ruth ask about directing and that Mealing has directed some episode of Casualty. She also directed a short film titled Another Man's shoes. She also directing a film which is still in post-production
Mealing has been married to screenwriter Richard Sainsbury since 1998, they have two sons, Otis and Milo, They live on a farm in Lincolnshire. Paul O'Grady and Charlie Condou are close friends of Mealing and are godfathers to her sons. She has appeared on The Paul O'Grady Show on several occasions, sometimes with her sons.
After the birth of her first son, the desire to find out more about her background became "hard to ignore"; she also wanted him to "know his heritage". Investigations took Mealing to New York, where she eventually found her birth mother, a model for Biba in London during the swinging sixties. She discovered that her biological father was a half-Sierra Leonean poet and activist. She gets on well with her mother and takes the children to visit her in New York but her father died some years earlier. She also found out that she has a sister, a year younger, also adopted in Britain. Her sister did not know of the relationship until she was 16, but had watched Mealing in Grange Hill, with people saying 'you look like that girl on TV'. Now close, when they first met their similarities were unbelievable — "we talk the same, walk the same, even our actions are the same".
With a desire to reconnect with her roots and acknowledge her father, and as an ambassador, Mealing has worked with Save the Children in Sierra Leone. She filmed a documentary about Kroo Bay — a slum built on the rubbish discarded by Freetown — saying: "It’s the worst place in the world you could grow up as child. One child in four will die before they reach five years old."
The day after giving birth to her second son, Mealing was diagnosed with breast cancer. She has since made a full recovery. Mealing was asked to be an ambassador for Breast Cancer Care in early 2010. She has developed a close bond with the charity. "When I was diagnosed the first leaflet I received was from Breast Cancer Care. They have been there for me ever since. I am deeply honoured to be given a chance to give something back to them." After losing a close friend to breast cancer early the same year Amanda decided to dedicate a JustGiving page to raise money in memory of her friend. She ran the 2012 London Marathon on her 45th birthday for Breast Cancer Care and finished in a time of 4hr 44min 26sec.
Since 2015, Mealing has been a Patron to the Nationwide Association of Blood Bikes, and is running the Great North Run in aid of the charity.