The new store is part of a wave of gentrification that has also brought the Ace Hotel, Target and a slew of other retailers downtown.
The Austin, Texas, chain will open the 41,000-square-foot store inside a luxury apartment complex at 770 Grand Ave. It will service a neighborhood that has increasingly attracted an affluent and hip crowd -- a prime customer base for the high-end supermarket.
Whole Foods executives and Los Angeles City Councilman Jose Huizar will discuss details with the media outside the construction site Friday morning.
Whole Foods said the new market will bring more than 150 jobs to the area.
The company currently operates 399 stores in the U.S., Canada and Britain.
When Whole Foods announced it would open a downtown store back in 2013, the company said it had been searching for the right location for nearly a decade.
"We know that access to natural and organic foods in the neighborhood has been challenging," Patrick Bradley, president of Whole Foods Market Southern Pacific Region, said in a statement.