Los Feliz lies north of East Hollywood and just south of the Santa Monica Mountains, adjacent to the neighborhoods of Hollywood and Silver Lake. Home to the southern face of Griffith Park, the district includes the Griffith Observatory and the Greek Theatre. Los Feliz is bordered by Hollywood Boulevard to the south, Hyperion Avenue to the southeast, Griffith Park to the north, the Los Angeles River to the east, and Western Avenue to the west. It is traversed by Los Feliz Boulevard.

Mickey Mouse was "born" in Los Feliz, Walt Disney drew his first image of the now-legendary character in the garage of his uncle's house which was located on Kingswell Avenue between Vermont and Rodney. Disney's first animation studio was on Kingswell Avenue, just down the street from his uncle's house and east of Vermont. The second, larger studio was located at the corner of Griffith Park Blvd and Hyperion Avenue, on the Silver Lake side of the Los Feliz-Silver Lake boundary.

Los Feliz was also home to many other early studios, such as that of D. W. Griffith; the site is currently home to The Prospect Studios (formally known as First National-Warner Brothers and more recently ABC Television Center), at the intersection of Prospect Avenue and Talmadge Street. On Sunset Boulevard was Monogram Pictures (currently KCET public television), where early Charlie Chan movies were filmed, as well as "The Hurricane" starring Dorothy Lamour and the camp classic "Johnny Guitar". (The western street from that movie remained until the mid 1980s when KCET razed the set to make way for a much-needed parking structure—but they threw a huge studio-wide party there on its final days.)

The neighborhood has historically been home to movie stars, musicians, and the Hollywood elite. It boasts some of the best known residential architecture in the city, including two homes designed by Frank Lloyd Wright: Ennis House and the Hollyhock House, and Richard Neutra's Lovell House.