The march resulted in a violent confrontation with police, including the smashing of CHP cruiser windows, and the shutting down of the 101 Freeway near downtown.
An estimated 500 to 1,000 people participated in the event, starting near City Hall and then marching through downtown.
Video: Protesters smash window of CHP cruisers near downtown LA
It appears the event was not cleared with city officials in advance as there was a minimal police presence in the area.
At one point, dozens of protesters wandered onto part of the 101 Freeway near downtown and surrounded a CHP cruiser.
The cruiser tried to escape the crowd and someone smashed the back window with a skateboard.
As the CHP car tried to flee, a man rode on the car's hood for a few seconds, then fell off and appeared to hit his head as he fell to the ground. He then remained motionless as a crowd gathered around him.
A second CHP vehicle tried to assist and was also surrounded and had its window smashed. That vehicle also left.
Crowds were blocking downtown streets in the area of Temple and Los Angeles streets as they carried signs and stood still in the intersection.
Downtown LA protester: "It's not right. We're sick of it."
The march was a reaction to the death of Floyd and video showing an officer placing his knee of Floyd's neck while he was handcuffed on the ground.
One protester talked to ABC7 about how disturbed he was about seeing the video of the George Floyd arrest.
"When I saw the video of George Floyd getting murdered in cold blood, I've never felt anything like that in my life, man," he said.
"To know there's so many people just trying to do the right thing and just make a life and live, and the police brutality that continues to happen to black people over and over in this country is unacceptable."
"To be out here in this peaceful protest and they have riot gear and rubber bullets like were terrorists? It's not right. We're sick of it. No justice, no peace."
Some in the crowd were also seen burning an American flag.
At the start of the protest, the crowds were packed tightly together, with few people observing social distancing. The use of masks appeared to be inconsistent.
Police were later able to get the crowds off the freeway. The crowd began thinning out later in the evening and no other incidents of violence were observed.
Video shows police officer kneeling on neck of George Floyd before his death