The three-alarm fire is out and hotel guests have been evacuated to the MGM Grand Garden, reports CBS affiliate KLAS-TV. The casino is closed.
No major injuries were reported, said Clark County spokesman Eric Pappa.
The fire, which was reported around 11 a.m., halted gambling at the casino as it spread from the center of the building across the roof. Fiery debris fell to the street below, and orange flames lapped at the casino's script sign.
Officials went door-to-door evacuating the hotel, said Gordon Absher, a spokesman for the resort's owner, MGM Mirage Inc.
Guests told KLAS-TV that people were shocked when they saw the smoke and heard fire alarms but the evacuation went smoothly.
Larry Wappel, 25, of San Pierre, Ind., said he and his brother, Eric Wappel, were in a room on the 30th floor when they heard housekeeping staff banging on doors and yelling "Fire, get out!" He said it took about 10 minutes to walk single-file down the stairs to get to ground level.
"There were a couple of ladies crying, but it was pretty calm," he said.
Another guest, Renza Badilla, 45, said she exited through the hotel kitchen to find burning debris and embers falling from the roof.
"I think people were shocked when they saw the smoke," said Badilla, who said she was in the buffet on the main casino level when fire alarms sounded.
Investigators were trying to determine whether the fire had simply burned the resort's facade or penetrated rooms in the upper floors, which contain suites. Guests were being taken the MGM Grand Garden Arena and employees were evacuated to the adjacent New York-New York hotel, Absher said.
There are reports that welders were working on the roof of the hotel, but the cause of the fire is not officially determined yet, reports KLAS-TV.
Huge crowds formed to watch the fire, and traffic on the Las Vegas Strip was gridlocked as streets were blocked off around the hotel.
The nearby resorts, Bellagio and New York New York were not evacuated.
The Monte Carlo Resort & Casino has 3,002 guest rooms and 211 suites. The resort, located on Las Vegas Boulevard, near Tropicana Avenue, opened in June 1996.
The 32-story casino-hotel modeled after the Place du Casino in Monte Carlo, Monaco, was a joint venture between Steve Wynn's Mirage Resorts and Circus Circus Enterprises.