In the early 1940s, John Entenza, the owner of Arts & Architecture magazine and Case Study Program founder, purchased 5 acres of land on a wooded bluff that was once part of Will Rogers' large estate. He sold 1.4 acres of this land to Charles and Ray in 1945. Their home's design was first sketched out by Charles Eames with fellow architect Eero Saarinen in 1945 as a raised steel and glass box projecting out of the slope and spanning the entrance drive before cantilevering dramatically over the front yard. The structure was to be constructed entirely from "off-the-shelf" parts available from steel fabricator catalogs. Immediately after the war, though, these parts were in very short supply. By the time the materials arrived three years later, much pre-construction time had been spent picnicking at and exploring the lot where the house would stand. After a period of intense collaboration between Charles and Ray, the scheme was radically changed to sit more quietly in the land and avoid impinging upon the pleasant meadow that fronted the house. Although Eero Saarinen did not have any contribution to the Eames House as built, he did co-design the Entenza House (Case Study House #9) with Charles Eames next door for John Entenza.

The new Eames House design featured a residence building and a studio building tucked into the landscape's slope, with an 8-foot (2.4 m) tall by 200 foot (60 m) long concrete retaining wall. The lower level of the residence features a living room with alcove, hall with closets and spiral staircase, kitchen, and utility space. The upper level holds two bedrooms and overlooks the double-height living room in mezzanine fashion. The residence's second story also boasts two bathrooms, multiple hallways filled with aluminum closets, and a wire-embedded skylight. The studio building has a similar mezzanine, but is much shorter in length. The studio's ground floor features a utility sink, bathroom, dark room for processing photographs, and a large open space with double-volume height. The upper floor was primarily used as storage, but occasionally became guest quarters. A courtyard was also introduced, separating the residence from the studio space. This revised scheme required only one additional beam. The 17 foot (5.1 m) tall facade is broken down into a rigidly geometric composition of brightly colored and neutral-colored panels between thin steel columns and braces, painted "a warm grey". Over time, painting schemes allowed the grey to become black. The entry door is marked with a gold-leaf panel above. Planted in the 1880s by Abbot Kinney,[2] an existing row of eucalyptus trees was preserved along the exposed wall of the house, providing some shading and a visual contrast with the house's bold facade.

As for the interior design, the Eameses' collection includes, among others: an Isamu Noguchi floor lamps, folk and Abstract Expressionist art, Japanese kokeshi dolls, Chinese lacquered pillows, Native American baskets, Thonet chairs, and numerous Eames furniture designs (some of which never made it past the prototype stage). The maximalist interiors were grouped by the Eameses in idiosyncratic tableaux and the home's interior decorating has sparked conversation of the Eameses "humanizing" modernism.

Of the twenty-five Case Study Houses built, the Eames house is considered the most successful both as an architectural statement and as a comfortable, functional living space. The brash sleekness of the design made it a favorite backdrop for fashion shoots in the 1950s and 1960s for publications such as Vogue. Perhaps the proof of its success in fulfilling its program is the fact that it remained at the center of the Eameses' life and work from the time they moved in (Christmas Eve 1949) until their deaths. Eames House is one prominent architectural example with the influence of the De Stijl Movement outside Europe. The sliding walls and windows give it the trademark versatility and openness of the De Stijl Movement. After the Eameses died, the house was largely unchanged.