He will leave the position at the next AGM of the Church Commissioners scheduled for June 2017. He was knighted for his services to the Church in 2015.
The role of First Church Estates Commissioner involves overseeing the management of the Church of England's £7 billion investment portfolio.
Her Majesty The Queen will have to approve the next person to take the job.
Sir Andreas said: "After fifteen years service I think it appropriate and sensible to look towards an orderly handover to a successor.
"I am proud to be leaving the Church Commissioners at a time when we continue to enjoy robust and sustainable growth, while contributing in a substantial and meaningful way to the ongoing operation of the Church and its ministry."
In May the Church of England confirmed it made a return of 8.2 per cent on its billions of pounds of investments last year.
That well exceeds the two per cent target set by the Church Commissioners.
After taking account of expenditure, the fund has grown from £2.4bn at the start of 1995 to £7.0 billion at the end of 2015, the Church said.
Bishop of London, Dr Richard Chartres, Deputy Chairman of the Board of Governors of the Church Commissioners said: "Andreas Whittam Smith has been an outstanding First Church Estates Commissioner.
"He has overseen the growth of the endowment and steered the organisation through numerous turbulent economic cycles, most notably the financial crisis of 2008.
"Under his leadership the Church Commissioners have led in responsible investment and in engaging with businesses on a wide range of economic and social issues."
