He taught as a professor of Tibetan Studies at the University of Washington and served as the first chair of the Department of Asian Languages and Literature.

Today, it is an almost universally adopted scheme for accurately representing the orthography of Tibetan in the Latin script, and is commonly referred to as the Wylie transliteration.

Following the People's Liberation Army's takeover of Tibet, Wylie invited the first group of Tibetan refugees to Seattle in 1960, courtesy of the Rockefeller Foundation.

Upon his death, the 14th Dalai Lama remarked, "Dr. Wylie's strong and genuine feelings for the Tibetan people and their just cause will long remain deeply appreciated.

"[4] At the memorial service on 9 October 1984, Jigmie Yuthok speaking on behalf of the Seattle Tibetan Community said, "As a scholar in the truest sense of the word, whose life-long research in the histories of Tibet and China led him to discern fact from fiction, he stood up for the truth of Tibet's independent status and spoke out at every opportunity even in the face of overwhelming opposition from numerous vested interest groups.