Jay Sarno, owner of the Cabana Motel chain, stopped in Las Vegas in the early 1960s while on a trip to scout a new location for one of his motels in Northern California. Sarno, who wanted to build a large resort hotel someday, liked the cheap land and potential he saw on the Las Vegas Strip. He decided to stay and build Caesars Palace, a resort that would set new standards for modern hotel-casinos, providing a mixture of opulence and overindulgence that many would come to view as a symbol of the Las Vegas strip.

Sarno's vision for Caesars Palace included a luxurious, Greco-Roman themed hotel-casino where customers would be pampered and feted like the Ancient Roman Emperor Caesar, hence "Caesars Palace," with no apostrophe. He secured a $10.5 million loan from the Teamsters Union Central States Pension Fund, controlled by James "Jimmy" Hoffa, the corrupt Teamsters leader who was associated with organized crime. In 1962, Sarno acquired thirty-four acres in the mid-Strip area, across from the Flamingo Hotel, from investor and former aviator Kirk Kerkorian. Sarno's main partner in the project was his friend, Nathan Jacobson, of Baltimore.

With noted resort architect Melvin Grossman, Sarno, inspired by what he saw on a research trip to Europe, designed an extravagant property that cost a then-record $19 million. He imported tons of Carrera marble from Italy and commissioned artists to fashion faux Roman-style statues and friezes. He installed a series of eighteen fountains, surrounded by the hotel's 135-foot long front entry and exit roads, beside a pair of hotel wings lined with Roman columns. Sarno designed the casino's unusual oval shape. Below the hotel's front marquee, he placed life-like color statues of Roman guards.

When Caesars opened with a three-day, $1 million party in 1966, many saw it as the first true luxury resort in Las Vegas, surpassing in quality other well-known Strip hotels such as the Tropicana and Desert Inn. Sarno hired costumed actors to portray Caesar and Cleopatra to greet guests, a tradition that would continue at the hotel that eventually became Las Vegas' most famous resort.

Caesars Palace included 700 hotel rooms and expensive gourmet restaurants, such as the Bacchanal Room, where waitresses dressed like Roman goddesses and served multi-course dinners and free-flowing wine from long, narrow casks. The hotel's large rear pool was designed after the baths of ancient Pompeii. Its fourteen-story tower contained fancy regular guest rooms and lavish, two-floor open suites with Jacuzzi tubs that had windowed views of the Las Vegas Strip. Some of the suites were named after celebrities, such as actress Ann-Margaret, whose suite featured a round bed. Sarno sought out the top names in entertainment for his 800-seat Circus Maximus showroom, booking the likes of singer/actors Frank Sinatra and Barbra Streisand. The hotel's tiered lounge, Nero's Nook, included a reflecting pool.

Soon after it opened, Caesars was plagued by rumors that members of organized crime, such as Meyer Lansky of Miami and Sam Giancana of Chicago, were silent investors receiving illegal shares of the casino's profits. Sarno and Jacobson denied the allegations. The State Gaming Control Board investigated possible hidden mob involvement at the hotel throughout the late 1960s and the 1970s.

With their resort a big success, Sarno, Jacobson, and other investors decided to sell it in 1969 to brothers Clifford and Stewart Perlman, owners of the Lum's restaurant company in Miami, for $60 million. Sarno concentrated his efforts on his newest property, the Circus Circus. The Perlmans created the hotel company Caesars World, investing $25 million to renovate Caesars, including the addition of a 280-room tower.

In the 1970s, the Perlmans encountered licensing problems with the Gaming Control Board when the U.S. government alleged that mobsters from New England and Chicago, former Caesars employees, and others may have skimmed money from the casino to pay hidden investors and avoid taxation. The agency found no wrongdoing by the Perlmans. In 1980, Caesars World added a 600-room hotel building, the Fantasy Tower, and convention space just off the Strip. Caesars served as the site for celebrity tennis tournaments and, starting in 1981 when a racetrack was built on its grounds, four grand prix auto races.

In the early 1990s, Caesars added the Forum Shoppes at Caesars, a decorative indoor mall with upscale restaurants, designer clothing and jewelry stores, and a moving Roman sculpture attraction. The Perlmans subsequently expanded the shopping area to include more stores and restaurants. The hotel company ITT-Sheraton bought the hotel in 1995 and later spent $650 million to improve the property.

Two years after its purchase, ITT-Sheraton debuted a 1,100-room hotel building, the Palace Tower, and a new ballroom. The hotel investment company Starwood Hotels & Resorts acquired the hotel later that year and in 1999, sold Caesars and its other casino properties in Las Vegas and New Jersey for $3 billion to Park Place Entertainment, owner of Bally's Las Vegas, the Flamingo, and other Las Vegas hotels.

In 2003, Park Place opened a new showroom at Caesars at the former site of the old Circus Maximus. The Colosseum Theater, with 4,500 seats and an enormous stage, served as the venue for Canadian singer Celine Dion. Elton John also appeared regularly in the theater. Park Place changed its name to Caesars Entertainment, Inc., in 2004, and in 2005 merged with Harrah's Entertainment, a major Las Vegas casino company, in a money and stock deal worth $9 billion.