No car will ply on the 6.5-km stretch between the 17th century Red Fort in Old Delhi and India Gate, a World War I monument, in the heart of the capital on Thursday.
Some 84 lakh vehicles ply in Delhi every day, contributing to its chaotic traffic and worsening quality of air.
Between 7 a.m. and 12 noon, shuttle buses will run on the stretch.
Delhi's Transport Minister Gopal Rai admitted to IANS that "there is not much the government can do about pollution except organising such events.
"It is up to the people to use more and more public transport," Rai said.
"The day is largely symbolic. We will will not be able the assess the reduction in pollution on that stretch."
The minister has announced that Delhi will mark a Car Free day on the 22nd of every month. The routes will be decided by the city government.