Louise Bethune graduated from the Buffalo Central High School in 1874.
In 1876 she took a job working as a draftsman in the office of Richard A. Waite and F.W. Caulkins, well known architects in Buffalo, New New York At the time, it was more common to learn architecture while working for a firm rather than in a classroom.
In 1881, after five years in Waite's office, she opened an independent office partnering with Robert Bethune in Buffalo, earning herself the title of the nation's first professional woman architect. She later served a term as a vice president of the Western Association of Architects. She was named the first female associate of the American Institute of Architects in 1888 and in 1889, she became its first female fellowship
In 1891, she refused to compete in a design competition for the Women's Building at the World’s Columbian Exposition in Chicago because men were paid $10,000 to design buildings for the fair while the women got only $1,000.
Bethune designed mostly industrial and public buildings. She disliked working on residential projects because they paid poorly. She is especially known for designing public schools. Sadly, much of her work has since been demolished.
Bethune was elected a member of the Western Association of Architects (WAA) in 1885.
On December 10, 1881 Louise Blanchard Bethune married Robert A. Bethune.