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Grimsley High School was formerly known as Greensboro Senior High School. The name was changed to Grimsley High School on July 1, 1962. George Grimsley was the superintendent of schools in 1899.
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Greensboro High School opened in the fall of 1899, making it one of the first public high schools in the state of North Carolina.
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In the early 1920s, the athletic teams were known as the Purple Whirlwinds, and the school colors were purple and gold. In 1951, students voted to change the school colors to navy blue and white, and the Purple Whirlwinds became the Whirlwinds, which was eventually shortened to the Whirlies.
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The school opened at its current location on Westover Terrace on September 9, 1929, with a student body of 1300.

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Torchlight, the Grimsley chapter of the National Honor Society, is the oldest chapter in North Carolina.
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The Senior Tea, given by the faculty to honor the graduates, has been given every year since its beginning in 1940.

Grimsley's alma mater was composed and written by Herbert Hazelman in 1949. Mr. Hazelman was the Grimsley Band Director for 40 years. The music building is now named in his honor.

The school stadium, which seats 10,000, was completed in 1949.It was renamed the Robert B. Jamieson Stadium in 1975, when Coach Jamieson, athletic director with 42 years service, retired. The main gym was completed in 1954. It has been recently renamed the Robert R. Sawyer Gymnasium in honor of Coach Sawyer, who took over as athletic director upon Coach Jamieson's retirement.

In 1958, Josephine Boyd became the first African-American to graduate from Grimsley High School. Grimsley was the first formerly all-white high school in the South to have an African-American graduate.

Grimsley is a five-time winner of the Wachovia Cup, given annually to the school in North Carolina having the best overall sports program.

In the fall of 1995, Grimsley became the first school in Guilford County and only the fourth school in North Carolina to offer the prestigious International Baccalaureate (IB) Diploma Programme.