She joins the 4m member Trust from her current role as permanent secretary to the Home Office. Previously, Ghosh held a variety of civil service roles including as permanent secretary to Defra between 2005 and 2010.
She will take over from Fiona Reynolds who is leaving after 12 years.
Ghosh said: "I have been an admirer of the Trust and its work all my life, and I am thrilled that I have been given the chance to be part of its future. I am delighted to be able to build on Fiona Reynolds' great work in setting the Trust's direction for the 21st century".
Chairman Simon Jenkins said: "The Board of Trustees is delighted that Helen will be the Trust's next director-general. The Trustees' strategy is to widen the Trust's appeal and grow its membership. Helen is a distinguished and energetic public servant. We are convinced she is ideal to lead the organisation through what is proving a challenging time. We all look forward to working with her."
Reynolds, who moves on to become Master of Emmanuel College, Cambridge in 2013, said: "I am delighted by Helen’s appointment. The National Trust is a fantastic organisation to work for and I wish her, and the Trust, all the very best for the future."