The Nail Brothers Café was a well-known restaurant and billiard parlor at 450 Sixth Avenue during the 1880's. Grace Nail Johnson was an African-American civil rights activist and patron of the arts associated with the Harlem Renaissance, and wife of the writer and politician James Weldon Johnson. Johnson was the daughter of John Bennett Nail, a wealthy businessman and civil rights activist. She is known for her involvement with the National Association for the Advancement of Colored People (NAACP), the Heterodoxy Club, and many other African-American and Feminist organizations.

On this site, in 1869, Edwin Booth opened a grand theatre to a design by Renwick & Sands in the Second Empire style. It was operated under the direction of actor-manager, Sarah Bernhardt. Bernhardt had relationships with both men and woman, most notably to Louise Abbéma.

The Fifth Avenue Theatre was designed by Francis H. Kimball. The original front facade at 31 West 28th Street had heavy terra-cotta decoration (what became the main entrance on Broadway was more subdued). In the 20th century, the theatre presented vaudeville, films, and burlesque. Eleonora Duse was known to have relations with both men and women. The legendary Italian actress had her New York premiere at this theater. In 1909 Duse retired from acting, and near to that same time she met and became involved in a lesbian affair with Italian feminist Lina Poletti, a former lesbian lover to writer Sibilla Aleramo. The two lived together in Florence, Italy for two years before ending the relationship.

The Grand Opera House/Pike's Opera House was associated with Josie Mansfield and Ella Wesner who were romantic partners.

Designed c. 1907 by McKim, Mead & White as a clubhouse, 120 Madison Avenue was originally built as the Colony Club, the first social club established in New York City by, and for, exclusively women. The interior was decorated by Elsie de Wolfe. During World War I, the original clubhouse was used first as a convalescent hospital, then as a nurses’ mobilization center. It was then taken over by the new Carroll Club for Catholic girls. In 1963 the building was purchased for about $500,000 by the American Academy of Dramatic Arts which still occupies it today.

Novelist Edith Wharton was born and raised at 14 West 23rd Street which was first built in the 1850's as a townhouse. Growing up in the Chelsea community, she later incorporated her upper-class upbringing into her literary works. In 1882, the site was altered by Henry J. Hardenbergh for commercial use.

The exquisite Queen Anne style Hotel Chelsea at 222 West 23rd Street, erected in the 1880’s, is associated with many remarkable women including Sarah Bernhart, Bette Davis, Frida Kahlo, Eileen Myles, and Janis Joplin. The "Portrait of Jason", a seminal documentary by Shirley Clark about the struggles of an African-American gay man, was filmed at the hotel in the years just before Stonewall, as was Andy Warhol’s “Chelsea Girls’ featuring trans superstar Holly Woodlawn. Ironically, Warhol’s would-be assassin, Valerie Solanas, lived here for a time as well.

The London Terrace apartment complex at 435 West 23rd Street encompasses an entire city block in the Chelsea neighborhood. Built in 1929 to a design by Farrar & Watmough for Henry Mandel, it has had many famous residents over the years. Some of its notable occupants included Susan Sontag, Annie Leibovitz, and Kate Pierson (of the B52’s).

Poet Elizabeth Bishop once lived at 418 West 20th Street.

From about 1959 to 1968, the Mattachine Society of New York, an early and leading American homophile group, was based out of the Chelsea neighborhood.

The Church of the Holy Apostles at 296 9th Avenue was involved in all kinds of progressive causes, including women’s liberation and women’s issues.

The Women's Liberation Center was located at 243 West 20th Street in a former firehouse. The Lesbian Switchboard, a hotline for lesbians seeking information and support, was run out of this building for many years. As Chelsea began to prosper again, New York City decided that they wanted to sell off their properties and it was resold to a women's nonprofit.

Formerly at 69 West 14th Street. From 1959 - 1963 The Living Theatre, directed by Judith Malina and Julian Beck, occupied floors two and three. Merce Cunningham had his dance studio on the top floor, which is where Robert Dunn taught the composition classes that launched the Judson Dance Theater. In 1977 Peter Saul, who once danced in Merce’s company, taught ballet classes in this studio.

Penn South, or the Mutual Redevelopment Houses, was sponsored by the International Ladies' Garment Workers Union. It was also the home of Bayard Rustin who organized with many women activists.

The National Gay Task Force headquarters was formerly located at 80 5th Avenue.