Born in Malta, De Bono studied at St Edward's College and subsequently gained a medical degree from the Royal University of Malta. Studying at Oxford as a Rhodes Scholar, he gained an honours degree in psychology and physiology and a D.Phil in medicine. He went on to complete a PhD at Cambridge, and to faculty appointments at Oxford, London, Cambridge and Harvard. He is married and has two sons, and has resided on the Channel Islands for over a decade.

In 1969 De Bono founded the Cognitive Research Trust (CoRT) which continues to produce and promote material based on his ideas.

He has written "65 books with translations into 37 languages". He has spent the last 30 years teaching thinking, including working with governments, corporations, organisations and individuals, speaking publicly or privately on many matters. He has started to set up SITO - the 'Supranational Independent Thinking Organisation' based in Malta, which he describes as a "kind of intellectual Red Cross".

De Bono has detailed a range of 'deliberate thinking methods' - applications emphasizing thinking as a deliberate act rather than a reactive one. His writing style is simple and clear, though often criticised for being dry and repetitive. Avoiding academic terminology, he has advanced applied psychology by making theories about creativity and perception into usable tools. A distinctive feature of De Bono's books is that he never acknowledges or credits the ideas of other authors or researchers in the field of creativity.

De Bono's work has become particularly popular in the sphere of business - perhaps because of the perceived need to restructure corporations, to allow more flexible working practices and to innovate in products and services. The methods have migrated into corporate training courses designed to help employees and executives 'think out of the box'/' think outside the box'.