Measuring 20m tall and 4m wide, it is located at a 5-way road junction near the station and Manchester's shopping and leisure districts.
The screen will be able to show high resolution live streamed video, rolling text, split screen formats and will be Bluetooth enabled.
City Gateway was formed this year by David Lamey, previously a director at the agency Media Campaign, and he has been joined by former Railtrack commercial advertising manager Yan Huybrecthts.
Further large scale digital screens are planned in key locations throughout the UK and Europe.
Huybrechts said: "This premium location will form the backbone of any high-profile digital advertising campaign."