If you are planning to go to Mandalay directly from Yangon, you have three options. The most comfortable, convenient and expensive one is to take a flight. The price (for two way ticket) is more expensive than a two way ticket between Bangkok and Yangon. The second, less expensive one is to use the train. The cheapest and most uncomfortable way to travel is by bus.
Buses from Yangon to Mandalay usually leave around 5 PM in the afternoon, and arrives to Mandalay the next morning around 9 AM. The buses are all air-conditioned, but some of the bus drivers may turn off the air cons once the leave Yangon. Most buses will also take passengers in the axle seats, which makes the bus very crowded. The buses will stop on the way for dinner and supper, usually around 8 PM and after midnight. The stop depends on the bus service. Food might be a little difficult for you to digest as this is always Burmese rice and curry. Food price is not included in the bus fare. The toilets at these restaurants are almost always dirty.
The road is OK for most of the way although it is quite bumpy. Burmese soap operas, karaoke or sometimes Burmese traditional Anyeint is shown on the bus, usually with unbearably loud sound. The road is usually bumpy, and the bus jumpy so it is difficult for a traveler to sleep well on the way. There is no toilet on the bus so don’t hesitate to go to the toilet even if the toilets are extremely dirty (which is true in some cases).
For a bus service, I recommend “Man Shwe Pyay” as the buses are newer and in better condition. They also open air con all the way and don’t have the axle seats so the bus driver cannot take any passenger on the way.