Hong Kong and Macau - Late night to Guangzhou

I will be arriving in Hong Kong at 8-9PM on DEC 14. What Is the best way to travel to Guangzhou from the airport?

Last direct coach departs at 10:15p. If you miss that, last coach to Huanggang departs at midnight - there MAY be late night coaches from there to GZ, though I am not 100% sure. After that, no easy way unless you hire a direct cross-border van.

How many hours does it take to arrive in Guangzhou from Hong Kong?

Assuming little traffic that time of the day and smooth crossing of the border for all passengers, I'll say about 3.5 hours for the bus trip. 45 min to the border, 30-45 min at the border, and two more to Central GZ.