The school's history dates back to the late 19th century, while the current building opened in 1968, with two additional wings added on later.

Guthrie High School competes in Class 5A of the OSSAA.

The Bluejays play at Jelsma Stadium which built during the 1930s at the site of an old train terminus, the stadium with its wall on the north side causes horseshoe-like wind conditions and it is known for being one of the most unusual places to play in Oklahoma as well as in the nation.

GHS won class 5A state championships in football in 2002, 2007, 2011 and 2013; basketball in 1954, 1956, 1968, 1969, 2008, and 2009.

The Bluejays also won a state championship in boys' track and field in 2009, a first for the track and field program in Guthrie.