"How can anyone not see that we are at the limits of our capacity of integration and that mass immigration is a cultural threat to European civilisation today," Wauquiez told a meeting of 1,500 people, including a number of MPs, in central France.
Wauquiez, who was elected Republicans leader in December last year, is on the right of his party and has been accused of taking up themes and phraseology dear to the far-right National Front (now the National Rally).
He appeared unfazed by that criticism at the meeting to mark the start of the new political season on Sunday, giving a speech that made it clear that migration will be a central plank in his party's platform in next year European parliamentary elections.
"The French refuse to become foreigners in their own country," he told an enthusiastic audience, adding that "something must be done to ensure that there is some civilisation left".
Migrant rescue boats
"We should no longer allow these boats to enter European ports," he declared.
Just over 60,000 people applied for asylum in France in the first six months of this year, up 16 percent on the same period last year.
Populism, censorship, taxes
Wauqiez, a graduate of France's exclusive ENA university, also laid into the use of the term "populist", first espoused by Russian revolutionaries in the 19th century but today often used to describe right-wing hard-line nationalists like Salvini or US President Donald Trump.
A "small milieu ... lectures the people on morality", he said. "They have even invented this word populism to justify censorship and silence everyone who does not think as they do."
With growth lower than expected and President Emmanuel Macron falling in the opinion polls, Wauquiez declared the "end of the mirage of Macronism".
"We must give the French their money back," he said, calling for planned tax increases, notably on petrol, should be scrapped and denouncing the decision to raise pensions and family allowances by less than inflation as "unfair".