Park spokesman Scott Gediman says Yosemite Valley - the heart of the visitor experience at the park - along with a mountainous, 20-mile (32-kilometer) stretch of California's State Route 41 will close.
The closure-which is supposed to last through Sunday, July 29-will also affect all hotels, campgrounds, and visitor services in Yosemite Valley and Wawona, Calif.
The blaze, known as the Ferguson Fire, has burned for roughly two weeks and encroached on the western boundary of the park, sending smoke into the Yosemite Valley where numerous park's most famous attractions are located.
Park officials ordered closure of Yosemite Tuesday due to the fire, effective at noon Wednesday.
"They closed Half Dome Village yesterday, and they said they were going to close the (Yosemite Valley Lodge) by 12 so everyone was to leave the park by 12", Vishal told KFSN-TV.
The Ferguson Fire, raging west of the park, had killed one Cal Fire worker and burned 41,576 acres as of Wednesday.
Hundreds of miles to the south, winds were absent over the fire in Southern California's San Jacinto Mountains.
Yosemite Valley - home to the tourist spots of Yosemite Falls, El Capitan and Half Dome - Wawona, the Mariposa Grove of Giant Sequoias and other areas of the park were closed on Wednesday July 25.
The last time the 7.5-mile-long (12-kilometre-long) valley was closed because of fire was 1990, he said.
Visitors are advised to "limit activity during the periods of poor air quality", the park said in a statement.
While a portion of Yosemite National Park is temporarily closed to visitors, over 50% of the Park is still open to explore. The glacial valley has been enveloped by a choking haze of smoke from the Ferguson Fire.
Over almost two weeks, flames have churned through more than 57 square miles (148 square kilometres) of timber in steep terrain of the Sierra Nevada just west of the park.
The conflagration is one of about 75 major wildfires burning in the United States in an unusually active fire season that has already scorched about 3.98 million acres, mostly in western states.
The blaze forced 3,200 people to evacuate in communities such as Idyllwild, Mountain Center and Lake Hemet as it destroyed five structures and threatened 2,100 homes, the agency said.
A firefighter died and seven others have been hurt battling the flames, which were 25 percent contained as of Wednesday afternoon.
"People are heartbroken", Rhonda Salisbury, CEO of Visit Yosemite / Madera County, told The Associated Press.
French Gulch resident Raquel Hines said she had two hours to evacuate and that others in the former mining town had as little as 30 minutes to leave.