The Strait was named by Vancouver for James Johnstone, master of the armed tender Chatham.

It is the preferred channel for vessels from the Strait of Georgia leaving to the north of Vancouver Island through the Queen Charlotte Strait bound for Prince Rupert, Haida Gwaii, Alaska, and the North Pacific Ocean, and for southbound vessels from those areas bound for the ports of Vancouver, Seattle and Tacoma.

Telegraph Cove and Robson Bight on Vancouver Island are along the strait near its north end and the village of Sayward on Kelsey Bay is near its midpoint.

During the summer months, the Strait is home to approximately 150 orcas, which are often seen by kayakers and boaters packed with tourists.

Scientists including Michael Bigg and Paul Spong have been researching the orcas in the Strait since 1970.