-Airplane: From Havana (2 flights per week, 1h and 50 min)
Bus: From Havana (13 hours). The price is approximately 44 usd/cuc
By Viazul (http://www.viazul.com/) you take the bus to Santiago de Cuba and then you can stay in Bayamo when the bus goes through this city. Viazul has 4 departures. One more option is the Varadero-Trinidad-Santiago de Cuba route, once the bus goes through Bayamo you can stay there. This route has 1 departure everyday.
To guarantee the trip you must make the reservation before the last day before the departure. Often, the last day before the trip all the tickets are sold. You can make the reservation from the site. Please confirm the price in the Bus Station.
Rent a Car is also an option. However, it is kind of complicated the procedure for making the reservation in Cuba. You should make the reservation online and some weeks before your trip.