Starting and finishing in Market Square, runners will pound the streets and Victoria Park as they complete their 10,000-metre run which will get under way at 10.30am on Sunday.
Organisers expect the first runner back at around 11am, with the course set to be shut and all road closures lifted between 12pm and 12.30pm.
Freedom Leisure, which organises the event, has told runners: "Wherever possible roads have been closed, sections are on disused railway track, and traffic has been limited on certain sections of the route.
"Please do not deviate from the designated route for any reason. This is not only a risk to you but to motorists that may still be using part of the roadway."
A number of roads around Stafford are being closed for parts of the morning to allow those taking part to pass through safely.
Road closures in the town are at:
Earl Street, 9.30am-11am
Newport Road (closed at the end of Bridge Street), 10.15am-10.45am
A34 Queensway: 10.15am-10.45am
Riverway and Lichfield Road junction, 10.20am-10.45am
Riverway (northbound), 10.20am-11am
Bedford Avenue, Mynors Street, Tithe Barn Road, Cambridge Street (no right turn into Corporation Street), 10.20am-11am
Corporation Street (northbound), 10.20am-11am
Crooked Bridge Road (no right turn into Corporation Street), 10.30am-11am
Portal Road junction, 10.30am-11.30am
Sandon Road junction, 10.30am-11.40am
There are also parking restrictions in place on Prospect road and Trenchard Avenue.