Hout Bay Main Road has been closed in both directions, between Disa River and Victoria Roads, after Imizamo Yethu residents protested for job opportunities, according to traffic officials.
On Monday morning, residents used waste bags and stones to block the main road.
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"Traffic is currently diverted via Valley Road", Cape Town traffic services spokesperson Maxine Jordaan said.
The City of Cape Town urged motorists to use alternative routes.
Police spokesperson Brigadier Novela Potelwa said Public Order Police, Hout Bay police station officials and the City's Metro police were keeping an eye on the protest.
"Approximately 300 protesters are burning tyres and barricading parts of the main road this morning," said Potelwa.
"The group is protesting about a lack of job opportunities for the youth in the area," she added.
Last Monday, 45 people were arrested for public violence, following sporadic protests across the City, many over land occupations.