The letter, signed by 16 of the 17 members of the President's Committee on the Arts and Humanities, criticised the "false equivalence" of Mr Trump's comments on the Charlottesville white supremacist rally, which left 32-year-old protester Heather Heyer dead.
Mr Trump controversially laid the blame for the violence on "many sides" and referred to "good people" who were among the white supremacist marchers.
"Reproach and censure in the strongest possible terms are necessary following your support of the hate groups and terrorists who killed and injured fellow Americans in Charlottesville," the letter says.
"Supremacy, discrimination, and vitriol are not American values. Your values are not American values. We must be better than this. We are better than this."
It goes on to urge Mr Trump to resign "if this is not clear to you."
Artist Chuck Close, author Jhumpa Lahiri, architect Thom Mayne and Jersey Boys actor John Lloyd Young are among the committee members to have signed the letter.
The committee, which since 1982 had advised the White House on cultural issues while running programs in schools, had never convened under Mr Trump, the
New York Times
reports.