Perth motorists have been warned to brace for major traffic disruptions as the HBF Run For A Reason shuts down roads across the CBD and surrounding suburbs on Sunday morning.

A network of road closures is now in place as thousands of runners hitting the streets for the annual charity event, with authorities urging drivers to plan ahead, use public transport and allow extra travel time.

William Street was closed from 11pm on Saturday as crews moved in to build the start line and install event infrastructure, with additional closures across the CBD and along the three run routes beginning from 4am.

Tow-away zones and parking restrictions have also been enforced along parts of the course, with motorists warned to check signs carefully before parking.

Roads affected include sections throughout the CBD and key surrounding corridors, though parts of St Georges Terrace and Adelaide Terrace westbound, Riverside Drive and Wellington Street will remain open with detours in place.

Authorities say the quickest route out of the CBD will be via Wellington Street northbound.

Drivers travelling south on the Kwinana Freeway are being told to detour east via Graham Farmer Freeway to Great Eastern Highway.

Those continuing south should travel via Canning Highway before rejoining the freeway at Canning Bridge.

All roads within the CBD and across the three event routes are expected to reopen by 1pm on Sunday.