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.
"This is a very important moment in the battle against the blight of addiction," Ms Touraine said.
One of the chief arguments for such places is that they put addicts - often poor, marginalised and sick - in touch with medics and social workers, who can help them.
Consuming substitute drugs in a clean environment also reduces the risk that addicts face from contaminated hard drugs bought from criminal dealers.
The Paris facility is in the Lariboisiere Hospital, and has a separate entrance. It will formally open its doors to addicts on Friday, and about 200 are expected there daily.
The addicts will have to register, but are not obliged to give their real name, and will not be pursued by police for going there.
The facility has a dozen cubicles affording some privacy to addicts when they inject. It is run by Gaia, an association that helps to treat addicts, and the annual running cost is put at €1.2m (£1.1m; $1.3m).
A leading Paris politician in the centre-right Republicans party, Philippe Goujon, is among the opponents who fear the initiative will undermine efforts to stop the hard drugs trade.
"We're moving from a policy of risk reduction to a policy of making drugs an everyday, legitimate thing. The state is saying 'you can't take drugs, but we'll help you to do so anyway," he told the daily Le Figaro (in French).
According to French health ministry data from 2011, more than 10% of drug abusers in France have HIV/Aids and more than 40% are infected with hepatitis C. Dirty needles and unprotected sex are the main routes for virus transmission.
Drug rooms exist officially in several European countries, including Switzerland, the Netherlands, Germany, Denmark and Spain, as well as in Canada and Australia.