In April 1636 Roger Williams left the Massachusetts-Bay colony and headed south, settling first on the east bank of the Seekonk River and later, when Massachusetts asserted territorial rights to this region, on the west bank. He named this site Providence. Williams's immediate reason for seeking new territory was, of course, religious freedom: his own Baptist beliefs did not sit well with the Puritan theocracy of the Massachusetts-Bay. The religious separatism present at the very birth of Rhode Island left a permanent legacy of political, economic, and social separatism in the state.

Although Roger Williams had negotiated with the Indians for his plot of land at Providence, the native population of Rhode Island did not fare so well thereafter. King Philip's War (1675–76) was devastating to both sides, but particularly to the Indians (Narragansetts, Wampanoags, Sakonnets, and Niantics), who were nearly wiped out, their pitiful remnants huddled together on a virtual reservation near Charlestown. The rebuilding of the white settlements that had been destroyed in Providence and elsewhere was slow but certain; from now on it would not be religious freedom or Indian warfare that would concern the white colonists, but economic development. In the eighteenth century the four Brown brothers (John, Joseph, Nicholas, and Moses) would be among the leading entrepreneurs in the Colonies. It is, however, a stain on Rhode Island's record that it was one of the leading slave-trading states both before and just after the Revolution, its many merchant vessels (some of them privateers) carting away hundreds of thousands of slaves, mostly from the West Indies. Relatively few ended up actually in Rhode Island; most that did so worked on large plantations in the southern part of the state.

Much to the chagrin of Lovecraft's Tory sentiments, Rhode Island was a spearhead of the Revolution, and people here were more united in favour of independence than in the other colonies. Stephen Hopkins, provincial governor of Rhode Island for much of the period between 1755 and 1768, was one of the signers of the Declaration of Independence. Separatist to the end, however, Rhode Island refused to send delegates to the Constitutional Convention and was the last of the thirteen colonies to ratify the Federal Constitution.