The male giraffe, named Benito, began his roughly 2,000km journey from Ciudad Juarez near the Mexican-US border to the Africam safari in the central state of Puebla, AFP reported.
According to zoo management, he will live with other giraffes in conditions closer to his natural environment.
"It is important that Benito is in favorable conditions, in a temperature-controlled enclosure, with all the food he needs," said Africam Safari Director Frank Camacho.
"We will include Benito in a very large herd, very diverse, where there are adults and young animals," he added.
The journey in a special trailer, accompanied by a team of experts, is expected to take around 50 hours in total.
The move follows a campaign by conservationists who have criticized inadequate living conditions in Ciudad Juárez, where the giraffe are at the mercy of extreme temperatures.
In mid-January, a judge ordered Benito sent to Puebla.
"Today is a very happy day for us," said Maria Ruiz Varela, a member of the Save Benito campaign.
"This is the culmination of almost nine months of hard work trying to inform the citizens and ask the government to listen to our pleas and allow Benito to go to a sanctuary, to a better place where he can have a good quality of life she added.
The campaign was backed by the US-based animal rights group People for the Ethical Treatment of Animals (PETA), which urged its supporters to "talk about a lone giraffe in Mexico".
She stated that Benito lived alone in an "enclosure littered with rubbish, without grass, shade and proper shelter in a region with extreme climatic conditions". /BGNES