Woodvale Construction in Omagh has a struck a £28m deal to deliver the works, with the Department of Education approving the award of the tender.
Construction will begin on the new school in Spring 2022 and is expected to take 30 months to complete.
Announcing the key milestone, Education Minister Michelle McIlveen said: "I am delighted to make this much anticipated £28million announcement, which is part of a total £34million capital investment in this new build for the school.
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"This important project funded by my Department, will provide state-of-the-art facilities for the school which caters for children aged 3 to 19 years with profound and multiple, severe and moderate learning difficulties.
"The new modern accommodation which I know will be welcomed by the Principal, Board of Governors, staff and pupils, will provide an improved learning and working environment at Ardnashee and will have a positive effect for everyone for many years to come."
When completed, the new build school will provide accommodation for a total enrolment of 275 pupils.
Ardnashee School & College is a controlled special school in L'Derry, which was formed in September 2014 through the amalgamation of Belmont House School and Foyle View School.
The Minister added: "I have no doubt that everyone in the school is looking forward to see the ongoing construction of the new school.
"Not only is this great news for the school community, this investment will also be welcomed by the construction industry by providing employment and a much needed boost for the local economy."
