The opening of the Flamingo Hotel in late 1946 signaled the beginning of the modern era of Las Vegas hotel-casinos on Highway 91, later known as the Strip. The Flamingo set a new standard of luxury for hotel guests and became the first of many stylish casino resorts constructed on the Strip after World War II.

The originator of the Flamingo was William R. "Billy" Wilkerson, a former owner of six Los Angeles nightclubs including the famous Ciro's on the Sunset Strip. Wilkerson was also a heavy gambler in Las Vegas, impressed by the potential he saw in the isolated desert town. In 1945, he purchased a thirty-three acre parcel on Highway 91, determined to build a new kind of lavish casino resort.

Wilkerson hired Ciro's architect, George Vernon Russell, and Tom Douglas, a well-known Hollywood interior decorator, to design buildings including a casino, a Parisian-themed showroom, nightclub, athletic club, steam rooms, swimming pool, hotel, and a Parisian-style restaurant for European chefs, all with full interior air-conditioning. Also among the plans were retail stores carrying French-made jewelry, thirty bungalows for high-end visitors, bidets in all the bathrooms, and the first golf course associated with a casino in Las Vegas.

Wilkerson wanted to build the town's largest hotel—with 250 rooms—surpassing the 110-room El Rancho and 107-room Last Frontier. To keep the minds of customers on gambling, he directed there be no windows or clocks on the walls, and designed a floor plan that required people to walk through the casino to get to the hotel. Wilkerson, who liked exotic birds, called his Las Vegas creation the Flamingo, based on the lanky, pink flamingos he once encountered on a trip to Florida.

Construction began in November 1945. With building costs estimated at $1.2 million, Wilkerson received a bank loan for $600,000 and another $200,000 from his friend Howard Hughes. Still short, the inveterate gambler foolishly tried to win extra investment money, and lost more than $200,000 playing craps in Las Vegas. Lacking the funds to continue, he accepted a $1 million investment from New York underworld figure Harry Rothberg. Rothberg and his organized crime associates Meyer Lansky, Gus Greenbaum, Benjamin "Bugsy" Siegel, and Moe Sedway became silent partners in the still-unfinished development.

Siegel, friendly with Wilkerson since the 1930s, joined the project as a representative of the new partners. The collaboration lasted until, with Lansky's blessing, Siegel forced Wilkerson to surrender creative control and remain only a shareholder. In June 1946, in order to run the Flamingo, he appointed himself president of his Nevada Projects Corporation.

Following a series of setbacks, the Flamingo finally opened with only 105 rooms, on December 26, 1946. Las Vegas had never seen such opulence, from the landscaping that featured imported Oriental date palm and Spanish cork trees to Siegel's tuxedoed staff, meant to attract wealthy clients in formal attire. Despite its lavish amenities, few customers showed up in the casino, including local residents, who favored the more casual, western saloon-like downtown properties.

Within weeks, mounting shortfalls, insufficient hotel rooms, and construction costs approaching $4 million forced Siegel to close the Flamingo. He reopened the resort on March 1, 1947, after completing the guest rooms with substantial loans from his organized crime associates.

Slowly, the property began to show a profit, but Siegel's mob investors grew impatient when he refused to repay their loans in a timely fashion. Taking matters into their own hands, they ordered Siegel's assassination in June, 1947. Sedway, Greenbaum, Lansky, and their associate Morris Rosen, quickly seized control. They purchased the Flamingo from Siegel's Nevada Projects Corporation for $3.9 million, renamed the resort "The Fabulous Flamingo," and hid their organized crime backgrounds by having a gaming license issued to their manager and "front man," Sanford Adler. Greenbaum replaced Adler in 1948, steering the Flamingo to a profit of $4 million in his first year.

In the 1950s, the Flamingo served as the venue for top-name entertainers. It enjoyed high name recognition, becoming the favorite resort among most high rolling gamblers even as other properties were being built on the Strip. Greenbaum, suffering from back problems, drug addiction, and gambling losses, decided in 1955 to leave the Flamingo for his home in Phoenix, Arizona, but he soon returned to operate the new Riviera Hotel on the Strip. With the hidden backers still involved, Thomas Hull, who had built the El Rancho fourteen years earlier, led thirty local investors to buy the Flamingo for $7 million.

Under newly-appointed president Albert Parvin and his company, Parvin-Dohrman, the Flamingo refurbished its show stages and in 1958 added 92 rooms. Two years later, Parvin and other shareholders in the Flamingo—including actor George Raft and singer Tony Martin—sold controlling interest in the resort for $10.6 million to Morris Lansburgh, Sam Cohen, and Daniel Lifter, all hotel operators in Miami Beach. Privately, Meyer Lansky, living in Miami, received a $200,000 finder's fee for putting the sale together. A decade later, Lansburgh and Cohen were convicted and given one-year prison sentences on charges related to skimming casino proceeds, estimated at $10 million, from the Flamingo. Lansky, whose finder's fee was paid in installments by the defendants during the skimming, was also charged but not convicted.

In 1967, Kirk Kerkorian, builder of the nearby International Hotel, bought the Flamingo from Lansburgh and Cohen for $13 million. Kerkorian had the hotel's signature champagne tower front sign torn down and he built a twenty-eight-story tower. Four years later, Hilton Hotels chain owner Barron Hilton agreed to buy the Flamingo and International hotels from Kerkorian, who remained a shareholder in both. Hilton added another tower in 1975.

By the 1980s, the Flamingo, known as the Flamingo Hilton, was one of the largest hotels in Las Vegas, with more than 2,250 rooms. The hotel opened a pair of guest room towers in 1994, including 200 privately sold timeshare units, which put the resort's room total past 3,600. A wildlife habitat with penguins and flamingos was added as part of $130 million in improvements.

In 1998, Hilton spun off the hotel-casino division of the worldwide chain, creating Park Place Entertainment, which took over the Flamingo, Bally's Las Vegas, and the Las Vegas Hilton (formerly the International hotel). Park Place, owner of Caesars Palace across from the Flamingo, in 2002 changed its name to Caesars Entertainment, Inc. In 2005, Caesars Entertainment sold the Flamingo and its other hotels to Harrah's Entertainment, Inc., for $9 billion.