Hawthorne Boulevard was named after Dr. J.C. Hawthorne, the cofounder of Oregon's first mental hospital. Originally named "U" Street, the road was renamed Asylum Avenue in 1862. In 1883 the privately-owned Oregon Hospital for the Insane was replaced by a new state-run facility located in Salem, today's Oregon State Hospital. The "distasteful" name Asylum Avenue was abandoned in April 1888 when the street was renamed Hawthorne Avenue by city ordinance in honor of Dr. Hawthorne. It was further renamed Hawthorne Boulevard in March 1933.
Neighbors organized and prevented a McDonald's restaurant from being built at the site of an abandoned fast food building. The abandoned building was replaced with condominiums and retail shops on the first floor.