"Normally, we have to travel through Miami or Mexico, but this time it's very convenient," said passenger Carlos Munroy.
The flight was once routinely operated by Continental, chartered to Cuba Travel Services, a direct weekly connection for Cuban-Americans with family members still living in Cuba.
In 2004, the Bush administration severely restricted travel to Cuba. Now that President Obama has lifted those restrictions, Cuba Travel Services hopes that many of the 100,000 Cuban-Americans living in California will take advantage.
"It's family unification. These people are going down to see their loved ones and that's what we're here to help them do," said Elyzza Cabezas, who works for the charter service.
Among the 55 passengers who boarded Tuesday's flight was 15-year-old Yuseinis Gutierrez of Cuba.
"I'm really excited," she said. "I'm going to go visit my dad and my family, my grandparents."
Travel restrictions still apply to Americans who do not have family in Cuba, or are not going there for business, news-gathering or study purposes.