Born in Bangalore, India, the only child of British immigrants (her Scottish father ran the Far East division of a US textile multinational; her Irish mother worked for the British High Commission in India), she was educated in India and Singapore until her teens, then at a Roman Catholic girls' boarding school in Derbyshire. She studied for a BA degree in history and politics at the University of Kent, Canterbury, where she met her husband Peter (the couple have three children and live in Berkhamsted).
On graduation she began training as a teacher, completing a year at Holland Park School. She then gained a master's degree in politics from the University of London, and subsequently joined construction group Costain. Offered a job on Kevin Kelly's Business magazine, she then applied to be a research planner at The Guardian, which she joined in 1986.
Moving to advertising sales, she was mentored by Caroline Marland. As she rose through the Guardian Media Group behind Marland, Management Today magazine called her "One of the toughest operators to have risen through The Guardian Media Group's ranks." After rising to become CEO of Guardian Newspapers Ltd (now Guardian News & Media Ltd) in August 2006, she became CEO of GMG. During her tenure the Manchester Evening News and regionally based business were sold to Trinity Mirror, and a 49.9% stake in Trader Media Group was sold to Apax Partners, in a deal that valued the business at £1.35bn.
McCall was a non-executive director of Lloyds TSB (2008–2009), New Look (1999–2005, a position to which she was reappointed in 2010); and Tesco (2005–2008), a position from which she resigned after Tesco sued The Guardian for libel. She was chair of the Business in the Community project Opportunity Now, and has also acted as President of Women in Advertising and Communications London.
McCall was named Veuve Clicquot Business Woman of the Year in April 2008, and was appointed Officer of the Order of the British Empire (OBE) in the 2008 Birthday Honours for services to women in business.
On 24 March 2010, McCall's appointment as the next Chief Executive of easyJet was announced. She is said to prefer a "pragmatic approach to Human Resources rather than politically correct niceties".
In February 2013, she was assessed as one of the 100 most powerful women in the United Kingdom by Woman's Hour on BBC Radio 4. She is currently one of five female CEOs of a FTSE 100 Index company.
In June 2014, McCall was awarded a Doctor of Science Honoris Causa by Cranfield University in recognition of her outstanding contribution to the aerospace industry and her distinguished achievements in international business She was appointed Dame Commander of the Order of the British Empire (DBE) in the 2016 New Year Honours for services to the aviation industry.