 When King Philip's War broke out in 1675 (pitting many Native American tribes of southern New England against English colonists), Danforth was involved in some of the events of the war. Many colonists distrusted the Praying Indians (Christianized Indians living peacefully in communities on the outskirts of English towns), some of whom were attacked by mobs of English settlers seeking revenge for attacks on their communities. Danforth, along with Daniel Gookin and the Indian missionary Reverend John Eliot, was a vocal supporter of the Praying Indians, and worked to prevent some of these excesses, at some personal risk. In one notable instance Danforth was aboard a small boat with other colonial officials in Boston Harbor en route to Long Island to inspect facilities for Praying Indians who had been relocated their "for their own safety" when a nearby ship apparently intentionally rammed the smaller vessel. No one was injured in the incident, but all of the older officials were dunked in the cold waters of the harbor.
