Loreto Sixth Form College was chosen from 23 other Beacon Award winners by the president of the association's charitable trust, paralympic gold medalist Giles Long.
The Moss Side teenagers who took part in its "Adding Value in the Inner City" project earned A-level results that helped make Loreto the best college in the country on the added value league tables.
Students on average gain A-level results two grades higher than predicted from their GCSEs, and 85 per cent of them go on to university.
Mr Long said: "This project stood out for me because of its aim of providing a pathway to channel young people towards bettering themselves through education in an area of Manchester where the odds aren't necessarily in their favour.
"I am a big believer that talent is gifted irrespective of class, but it is the harnessing of that talent that is not only crucial for the individual, but for the nation as a whole. Loreto Sixth Form College seems to be filling an important gap where it is most needed."
The college said its approach was to create strong links with local schools and lower the barriers to achievement by recruiting students with minimum qualifications, then offering them advice, support and careful monitoring.
College principal Ann Clynch said: "It is wonderful that the work and commitment of staff and students, year on year, has been recognised in this most valued of Beacon Awards."
The Beacon Awards, now in their 17th year, recognise college achievement in a range of categories.
Loreto Sixth Form College won the category for delivery of level 3 qualifications, sponsored by the Department for Children, Schools and Families, before being selected for the Presidents' Award.