Passengers had to agree to adhere to some health restrictions when they boarded the ship.
Carnival Vista is the first ship setting sail Saturday. At full capacity, it can carry 3,934 passengers.
The last ship to leave out of Galveston departed in March 2020.
On July 15, the Carnival Breeze will also set sail from the Galveston port.
According to Carnival's website, all guests must be fully vaccinated and able to show proof. If you don't do this, you won't be allowed on the boat and will not be able to receive a refund.
Carnival guests will have to complete a health questionnaire before getting on the boat, and anyone with possible COVID-19 symptoms will have to get tested.
On the ship, masks and physical distancing are not required, but the cruise liner reminds guests to be aware of the regulations at ports along the way.
Galveston's local tourism took a huge $44 million hit last year when everything shut down.
RELATED: Unvaccinated people to pay more for some cruises
If you're not vaccinated, it might cost you more to cruise
About 3,600 local jobs are tied to the industry, so it's safe to say they are ready to set sail again.
If you're thinking about cruising, make sure you're aware of the cruise liner's rules. The requirements differ between each cruse liner.
Travel experts say you should also consider travel insurance, just in case you end up testing positive for COVID-19 before your trip.
"What about the quarantine and evacuation costs? Well, you know that that's the new clause they're writing into the travel right now," Don Depasquale with Cruise Planners said. "So that if you get stuck in Costa Rica, let's say, and you can't get back on the ship, this insurance will cover your accommodations until you're able to travel."
Follow Charly Edsitty on Facebook, Twitter and Instagram.
SEE ALSO: 2 passengers test positive for COVID-19 on fully vaccinated cruise ship
2 passengers test positive for COVID-19 on cruise ship that required vaccinations