Three people were killed and more than 175 injured in twin explosions Monday at the Boston Marathon.
"Whoever did this obviously did not know [expletive] about the people of Boston," Colbert said at the beginning of Tuesday's edition of "The Colbert Report" on Comedy Central.
"'Cause nothing these terrorists do is gonna shake them. For Pete's sake, Boston was founded by the pilgrims -- a people so tough they had to buckle their [expletive] hats on!"
He mentioned other tough Bostonians, such as the Red Sox and the veteran rock band Aerosmith.
"These maniacs may have tried to make life bad for the people of Boston, but all they can ever do is show just how good those people are," Colbert said.