Piers Morgan compared the 2014 No result to Scotland's recent loss against Japan in the Rugby World Cup, telling Nicola Sturgeon she needed to "suck it up".
The First Minister appeared on ITV's Good Morning Britain on Monday morning, where she confirmed her intention to fight for a second vote on Scotland breaking away from the rest of the United Kingdom.
Ms Sturgeon said she believed a repeat of the 2014 referendum would yield a different outcome this time round, as a result of the UK's imminent departure from the European Union.
Speaking live on air via video link from Aberdeen, where the SNP is holding its annual conference, she told hosts Piers Morgan and Susanna Reid that Scotland's voice was being "ignored" since a majority of Scots voted to remain in Europe.
However, her comments provoked the ire of Morgan, who pointed out that Scotland is a part of the United Kingdom and therefore democratically bound to adhere to the result that 52 percent of Brits voted for.
The former News of the World editor then said Sturgeon needed to "suck it up", comparing the referendum loss to Scotland's capitulation against Japan in the Rugby World Cup on Sunday.
He said: “You’re part of the United Kingdom which voted to leave the European Union.
"Everything you want is what people voted against. In a democracy, it's called losing.
"It's exactly what happened to your rugby team yesterday. They lost - suck it up."
Ms Sturgeon replied: "Absolutely - I lost the referendum in 2014. But I do believe in a democracy you're entitled to change your mind."
The First Minister made light of Piers' attempts to compare the referendum loss to the rugby result.
She added: "Rugby matches, as important as they are, particularly during a world cup, are not the same as the future of the country.
"The way Scotland is being completely ignored and disregarded, yes I believe we should have another opportunity to decide if we want to be an independent country."
During the same interview, Ms Sturgeon refuted claims by Morgan that a Yes vote would result in a possible hard border between Scotland and England, echoing the Brexit dilemma faced by the Northern Ireland and the Republic.
"We would continue to trade with the rest of the UK and the rest of the UK would trade with Scotland," she said.
Despite clashing on a range of issues, Morgan was full of praise for Sturgeon after the interview came to an end, stating she "exudes leadership" unlike her former Westminster equivalent, Theresa May .
Speaking from the ITV studios in London, he said: "I can't help liking Nicola Sturgeon."
He added: "Nicola Sturgeon, whether you like her or not has a clear idea of what she wants for her country."