The Deputy Prime Minister will mount a staunch defence of the Union in a speech to the annual CBI dinner in Glasgow.
The Liberal Democrat leader will call on the 600 business figures expected at the event to make their voices heard in the run-up to next year's referendum.
He will say: "This train is leaving the station - the debate is under way.
"So now is the time for you to express your views, to shape that debate, to influence and shape a modern and successful Scotland within a strong United Kingdom.
"A thriving business sector creates opportunity and diversity as well, of course, as the revenue on which our public services depend. So the future of devolution must evolve in a way that enables your success too."
The call follows claims members of the business community have been afraid to intervene for fear of an SNP backlash.
Rupert Soames, the chief executive of Glasgow-based Aggreko, last year claimed some business leaders remained silent because those opposed to independence had "brought down on themselves rains of bile and ire".
Mr Clegg will say: "As the debate moves forward, it is becoming increasingly clear that the SNP will say anything to get the people in Scotland to vote for independence. That they are trying to de-risk independence and make it seem less of a jump than it really is.
"But separating our family of nations - the creation of a new international border - would inevitably mean a drifting apart.
Sir Mike Rake, the new president of the CBI, will restate the organisation's position as "unconvinced" by the merits of independence. He will say: "The CBI has an interest as the outcome will have significant potential impacts on businesses and consumers in Scotland and across the whole of the UK."