The new Eastern High School will be located on land formerly used by Cardiff and Vale College's Trowbridge campus.
The new school and college for 11 to 18-year-olds is being jointly funded by the City of Cardiff Council and Welsh Government.
It is estimated to be ready for September 2017.
Councillor Sarah Merry said: "This represents a £25m council investment in the future of children growing up in the east of the city, and using Willmott Dixon to design and build the new facilities will ensure the best possible education for pupils and students in East Cardiff and the best value for money for the taxpayer."
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Willmott Dixon Managing Director for Wales, Neal Stephens, said: "We are delighted to be involved in this excellent new school for the city and given that so many of our staff live here, it will be something their children will benefit from too.
"Community will be a big focus for us and we will try whenever possible to use local labour and companies to build Eastern High."
Cardiff and Vale College Principal and Chief Executive Mike James said: "This development will create a fantastic facility that the whole community of East Cardiff will benefit from."
(LM)
