The firm will invest £10.5m in the site in a development joint venture with owner Tiger Developments.
Under the deal Interserve Construction will carry out £150m of building work for offices, shops, leisure facilities, an hotel and underground parking.
The site already has full planning, with tenants already signed up for the initial development phase including Tesco and serviced apartments provider Staycity.
Food chains Prezzo and Pret A Manger are already committed to the second phase, together with advanced discussions with other occupiers for a further 70,000 sq ft of retail and office space.
Adrian Ringrose, CEO of Interserve, said: “Edinburgh’s Haymarket site remains one of the best city centre developments schemes to be found anywhere in the UK.
“It will provide a strategic gateway for the city centre, linking seamlessly with one of Scotland’s busiest railway stations, as well as being adjacent to the city’s new tram network.
“The proposals for a mix of leisure, retail and office space, linked by open public spaces, will act as a catalyst to regenerate the commercial heart of the area as well as create jobs.
“Our involvement and financial commitment to this project underlines Interserve’s ability in creating value by structuring asset-based funding in combination with the design and delivery of large scale projects.”
Tiger will partner with Interserve in managing the marketing and development of the Haymarket site, building on interest already received in the scheme.
The Haymarket site is one of the city centre’s last remaining major gap sites.
The construction project will be delivered by Interserve’s local construction team, based in Livingston.
Around 250 Interserve employees will work on the project – employed either directly by the company, or by its local supply chain and specialist sub-contractors.