Dozens of people arrived Friday night at the Metropolitan Transportation Center in the city and set out at dawn on their way to the border with Guatemala.
Local media showed images of hundreds of migrants who began their journey on foot, others on buses or hitchhiking.
This is the first caravan of this year, with the most recent one forming in March 2021, though it was dissolved by Guatemalan authorities.
More Hondurans have been leaving the country over the past year as a result of the progressive lifting of restrictions aimed at containing the spread of COVID-19 pandemic.
Most migrants are fleeing poverty and violence in search of better opportunities.