East Midlands Airport is being closed for seven consecutive weekends while the runway is resurfaced.
Clic Sergeant, which supports young people with cancer, organised for nearly 3,000 people to run two courses around the perimeter of the airport.
Runners passed maintenance and fire control centres which are so sensitive they were asked not to take pictures.
Andy Cliffe, managing director at East Midlands Airport, said: "The closure of the airport for runway maintenance only happens every 15 to 20 years.
"It therefore gave us the opportunity to host a family running event, which is ideal for people of all ages and abilities, as part of our work to support our chosen charity CLIC Sargent."
Fundraising manager Anna Finnegan said: "Last year CLIC Sargent supported over 600 families in the East Midlands.
"This is such a fantastic opportunity for people from the Midlands to get involved with, and we are thrilled that all participants will be encouraged to raise money for children and young people with cancer."
The airport is the UK's busiest freight airport but managers said the weekend closures would cause the least disruption.
It will be closed each weekend until the 17th December.
During the works, about 50,000 tonnes of material will be laid on the 2.9km (1.8 mile) runway, with 1,200 lights replaced.
A charity has used a rare airport shutdown to let thousands of runners access normally restricted areas.