In 1926, a westward extension of double-deck Wacker Drive increased development on the south riverbank. In 1927, Marshall Field and Company announced its plans to build on the north bank opposite Wacker Drive. Owned by Marshall Field & Co., the Merchandise Mart opened on May 5, 1930, just east of Chicago's original trading post, Wolf Point and the site of Chicago and North Western Railway's former Wells Street Station, abandoned in 1911 in favor of the Chicago and North Western Passenger Terminal. With the railroad's air rights, the site was large enough to accommodate "the largest building in the world". Removing the train yard supported the Chicago Plan Commission's desire to develop and beautify the riverfront. The building realized Marshall Field’s dream of a single wholesale center for the entire nation and consolidated 13 different warehouses. In 1945, the Merchandise Mart was purchased for $12.5 million by former Ambassador to Great Britain Joseph P. Kennedy, Sr., the father of future U.S. President John F. Kennedy. Later managed by Sargent Shriver, the building was owned for more than 50 years by the Kennedy family through Merchandise Mart Properties, Inc. until 1998, when MMPI was acquired by Vornado Realty Trust.

Large enough to have its own ZIP code, 60654, the Merchandise Mart was designed by the Chicago architectural firm of Graham, Anderson, Probst and White to be a "city within a city". Started in 1928, completed in 1931, and built in the same art deco style as the Chicago Board of Trade Building, its cost was reported as both $32 million and $38 million. The building was the largest in the world in terms of floor space, but was surpassed by The Pentagon in 1943, and now stands sixth on the list of largest buildings in the world.

James Simpson, president of Marshall Field and Company from 1923 to 1930 and chairman of the Chicago Plan Commission from 1926 to 1935, along with architect Ernest Graham turned the first shovels of dirt at groundbreaking on August 16, 1928. General contractor John W. Griffiths & Sons brought building construction into the machine age through the use of techniques "ordinarily used in the construction of big dams." Cement arriving by boat was lifted by compresse air to bins 75 feet above the ground, with gravel and sand delivered by railroad cars to conveyor belts and transfer elevators. Giant mixers provided wet concrete to skip hoists in vertical towers that were extended as the building rose. Continuously employing 2,500 men and as many as 5,700 men altogether, the construction project lasted a year and a half into the early months of the Great Depression. With a foundation footprint of nearly two square city blocks, the building required 29 million bricks, 40 miles of plumbing, 380 miles of wiring, nearly 4 million cubic yards of concrete, 200,000 cubic feet of stone, and 4,000 windows. Bethlehem Steel fabricated much of the 60,000 tons of steel. An estimated 7.5 miles of corridors and over 30 elevators were included in the construction.

Designer Alfred Shaw integrated art deco styling with influences from three building types - the warehouse, the department store and the skyscraper. A warehouse block stands as the 18-story bulk of the building. Ribbon piers define the windows, and the building's chambered corners, minimal setbacks, and corner pavilions disguise the edges of the mass and visually reduce bulk. The south corner pavilions are of greater height than the north corner pavilions. The building is open at the pedestrian level with bronzed framed display windows, typical of a department store, on the south, west and east boundaries. The 25-story central tower ascends with a peak in the form of a skyscraper, and rests in the southern half of the building. Deeply recessed portals occur between raised panels, and are adorned with medallions featuring the interlocked initials of the Merchandise Mart. The same logo occurs throughout the building. Fifty six American Indian chiefs circled the tower's crown, a reference to the site's history and Chicago's early trade activities. Three and a half feet wide by seven feet tall, the terra cotta figures were barely visible from the street, meant to be viewed from the upper floors of the skyscrapers planned to rise along the riverbank.

The lobby of The Merchandise Mart is defined by eight square marble piers, with storefronts in side aisles framed in embossed bronze trim. The green and orange terrazzo floor was conceived as a carpet: a pattern of squares and stripes bordered by over scaled chevrons inlaid with The Mart's initials. The chevron theme is continued in the column sconces lighting an ornamented cornice overhead. Referred to as "business boulevards", two wide 650-feet long corridors with terrazzo floors in the upper levels featured six and one-half miles of display windows. Building regulations specified identical entrances along corridors but tenants could personalize the individual floor space. With the exception of the corridors, elevator halls, and exhibition space on the fourth floor, the five acres of each upper floor was "raw space" with concrete floors.

After years of being used by hundreds of government offices moving to The Pentagon, the purchase was followed by a renovation creating office space on the lower floors and promoting use of the upper floors for home furnishing and apparel showrooms. The Merchandise Mart was modernized in the late 1950s and 1960s. The Native American chiefs were removed, destroyed and replaced with concrete plates in 1961, of minimal note to onlookers as skyscrapers did not rise on the north side of the river as predicted. In 1962, an entrance canopy was constructed over the south for vehicle use.In 1977, Skidmore, Owings and Merrill designed the Chicago Apparel Center, located on the east side of Orleans Street, which increased the Merchandise Mart’s total floor space to 6.2 million square feet. Making use of plazas, esplanades and overlooks employed the waterfront location for pedestrian pleasure. In 1988, Helmut Jahn designed an enclosed pedestrian walking bridge over Orleans Street connecting the Mart and the Apparel Center. After a 10 year, $100 million modernization in the late 1980s that included public utility upgrades, Beyer Blinder Belle's commission in 1989 was to create additional perimeter entrances and restore the display windows, main entrance and lobby. On the south facade, the drive-through canopy was removed and two smaller doorways aside the main entrance were added. Display windows, painted over during the earlier modernization campaign, were restored with clear glass to showcase merchant's wares. New main and corner entrances were added to the rear facade, and the loading dock that occupied the north portion of the first floor of the river level was removed in order to use the bottom deck of North Bank Drive. Improvements to the lobby included restoration of the original glass curtain wall over the entrance, shop fronts and reception desk using terrazzo floors and wall sconces influenced by the original design. The project was completed in 1991.

Jules Guerin's frieze of 17 murals is the primary feature of the lobby and graphically illustrate commerce throughout the world, including the countries of origin for items sold in the building. The murals depict the industries and products, the primary mode of transportation and the architecture of 14 countries. Drawing on years as a stage set designer, Guerin executed the murals in red with gold leaf using techniques producing distinct image layers in successive planes. In a panel representing Italy, Venetian glassware appears in the foreground with fishing boats moored on the Grand Canal and the facade of the Palazzo Ducale rises above the towers of the Piazza San Marco. "To immortalize outstanding American merchants", Joseph Kennedy in 1953 commissioned eight bronze busts, four times life size, which would come to be known as the Merchandise Mart Hall of Fame: Frank Winfield Woolworth, Marshall Field, Aaron Montgomery Ward, Julius Rosenwald and Robert Elkington Wood of Sears Roebuck and Company, John Wanamaker, Edward Albert Filene, and A&P grocery founder George Huntington Hartford. All of the busts rest on white pedestals lining the Chicago River and face north toward the gold front door of the building.

A heritage of lighting the structure finds the central and corner towers, along with the columns between each window on the setbacks, bathed nightly in an upwardly focused white light. Tradition dictates annual changes to green in mid-March for St. Patrick's Day and orange during the fall months around Halloween and Thanksgiving. Prominent events have found the behemoth lit in pink for Cancer Awareness Month. To note the 2006 Chicago Bears season, highlighted by reaching Super Bowl XLI, the building was lit with team colors, orange floodlights for the setbacks and blue floodlights for the towers. Red and green lights are used during the Christmas season. Nighttime lighting on the Mart typically matches the colors of antenna lighting on the Sears Tower and the colors used on the top floors of the Aon Center.