The city is home to around 40 international organisations as well as 476 NGOs, according to the Keystone-ATS news agency.
Many of these organisations have been heavily reliant on US funds, including to pay their staff.
Geneva canton’s economic affairs minister Delphine Bachmann had warned before Friday’s vote that many would be forced to carry out mass layoffs or be unable to pay employees.
“Layoff announcements affecting several dozen people have already been made,” Bachmann told the RTS broadcaster on Wednesday.
The International Geneva Welcome Centre, which supports employees of international organisations and NGOs, estimates that several hundred jobs are on the line, according to Keystone-ATS.