Transport mayoral committee member Brett Herron said road closures and parking restrictions would apply for a fun run on Friday and the half and ultra marathon on Saturday.
On Friday, the left lane of the M3 would be closed between Rhodes Drive and the University of Cape Town off-ramp, in a northbound direction.
Roads in Mowbray, Newlands, Claremont, Bishopscourt, Constantia, and Rondebosch would be closed at different times between 4.30am and 1pm on Saturday.
Diep River, Bergvliet, Retreat, and Lakeside roads would be affected between 6.30am and 8.15am.
From 7am to 10am, roads in Muizenberg, St James, Kalk Bay, Clovelly, Fish Hoek, Sun Valley, Steenberg, and Westlake would be affected.
Roads in Noordhoek and Hout Bay would be closed at different times between 7.15am and 2pm.
The city would host thousands of local and international runners.
The marathon contributed more than R260 million to the local economy.
“We would like to extend a warm welcome to all runners and visitors to the city and hope that they will take some time out to visit some of Cape Town’s many attractions,” said acting tourism mayoral committee member Ian Neilson.