He has had a distinguished business career leading some of the UK's most successful investment banks. A development economist by training, Lord Cairns was Chairman of Allied Zurich and BAT Industries plc and also Deputy Chairman and Chief Executive Officer of SG Warburg. He has also chaired Actis Capital LLP (formerly CDC Group plc), one of the largest emerging market venture capital operations, with investments in agriculture, financial services, industry and infrastructure in eighteen African countries.

Alongside Cyril Ramaphosa, Lord Cairns founded and chaired the Commonwealth Business Council at the request of former UK Prime Minister Tony Blair and President Thabo Mbeki of South Africa. The organisation continues to provide a platform for governments and the private sector to work together to increase trade and investment across the Commonwealth, with a particular focus on Africa.

Between 1981 and 1992, Lord Cairns chaired Voluntary Service Overseas, the organisation responsible for placing over a thousand volunteers each year on a range of education, health and infrastructure projects. Lord Cairns has also served as Chair of the Overseas Development Institute, which under his guidance more than doubled in size and significantly increased its range of work.