Garrison stakes much of his argument on the immorality of slavery. He argues this point in both religious and secular terms. While this might seem obvious to the contemporary reader, Garrison wrote at a time when there were widespread counterarguments to his position. It would have been common for his audience to read and hear opinions that held slavery to be utterly moral and justified, having a basis in both Biblical and legal tradition.

Garrison takes pains to assert a divine morality that is not specific to any religious denomination. He wishes, he says, “to derive the assistance of all religions” (Paragraph 5). Readers would have been aware that Quakers, Presbyterians, and (Northern) Baptists were often associated with abolition, though nearly every group had members on both sides. Rather than following religious dogma as a guide to morality, Garrison invokes the religious but ecumenical concept of natural rights (see below) to bridge religious differences. That people are “endowed by their Creator” with rights both acknowledges the divine origins of equality and also leaves room for disagreement over theological details. He also invokes the American Revolution, seen by many as a moral war of the oppressed against the oppressor, as a touchstone for his argument.