The controversial drug room was opened by Paris mayor Anne Hidalgo and Health Minister Marisol Touraine on Tuesday. It is near the Gare du Nord, a busy station where drug crime is common.
The users will exchange hard drugs like heroin and crack for substitutes, along with sterile injection kits.
Critics fear it could fuel drug abuse.
Ms Touraine said France had become the tenth country to set up drug rooms, which Switzerland pioneered in 1986. There are plans to open two more - in Strasbourg, eastern France, and Bordeaux in the south-west.