Born in Rhodesia, now Zimbabwe, Alexander McCall Smith was educated at CBC Bulawayo before moving to Scotland to study law. After returning to southern Africa to teach law at the University of Botswana, he returned once more to Edinburgh, where he lives today with his wife, Elizabeth (an Edinburgh doctor), and their two daughters Lucy and Emily. He was sometime Professor of Medical Law at the University of Edinburgh and is now Emeritus Professor at its School of Law. He retains a further involvement with the University of Edinburgh in relation to the James Tait Black Memorial Prize.

He is the former chairman of the British Medical Journal Ethics Committee (until 2002), the former vice-chairman of the Human Genetics Commission of the United Kingdom, and a former member of the International Bioethics Commission of UNESCO. Due to his late success as a writer these other commitments could not be continued.

He is an amateur bassoonist, and co-founder of The Really Terrible Orchestra. He is also the author of a testimonial in The Future of the NHS (2006) (ISBN 1-85811-369-5) edited by Dr Michelle Tempest.

He was appointed a CBE in the December 2006 New Year's Honours List. In June 2007 he was awarded the Honorary Degree of Doctor of Laws at a ceremony celebrating the tercentenary of Edinburgh University's School of Law.