"This would be the very worst time for Britain to take the enormous economic gamble of leaving the European Union," Osborne told the BBC broadcaster.
Last Saturday, Osborne argued that Cameron’s reform agreement negotiated with EU leaders presented the “best of both worlds,” including free trade benefits without the single currency costs and free movement without welfare abuses.
"In my judgment as chancellor, leaving the EU would represent a profound economic shock for our country," Osborne reiterated, vowing to do "everything I can to prevent that happening."
A number of Cameron’s cabinet members and allies have aligned themselves with the “out” campaign, including his predecessor Michael Howard and London Mayor Boris Johnson.
The British pound fell to below $1.40 for the first time in seven years on Wednesday, and the Fitch rating agency projected short-term economic costs should the United Kingdom leave the European Union.