The Conservative former Prime Minister said the UK would understandably be seen overseas as damaged and diminished.
Britain's place on the United Nations Security Council would be "open to doubt" and its voice on other international bodies weakened if there was a "yes" vote, he suggested.
He issued a stark warning to the SNP that it faced a decade-long fight to be admitted to the EU as a separate member state.
And he renewed his warnings over the impact of any referendum on the UK's membership of the EU - saying quitting Brussels would also represent a huge blow to influence.
Appearing before a House of Lords committee, the 70-year-old former premier cited boyband One Direction as one of the British exports which help give the country an enviable standing across the world.
Television costume drama Downton Abbey and singers Adele and Susan Boyle were also on his list of cultural successes which "reflect a rather favourable impression on Britain".
Alongside language, democracy, the rule of law, the monarchy, the BBC, the Financial Times and the City of London as a financial centre, they had helped create an unrivalled profile, he suggested.
But - giving evidence to an inquiry into the role of "soft power" - he launched his strong attack on the idea of Scottish independence, which will be put to the vote north of the Border in September 2014.