The palace released a statement expressing the royal couple's "immense joy" at the news.
Prince Albert, 56, and the former South African Olympic swimmer, 36, married in a lavish ceremony in 2011.
He has two other children - Jazmin Grace Grimaldi and Alexandre Coste, but as because they were born out of wedlock, they cannot be heirs to the throne.
The baby, which is expected at the end of the year, will be the first in line to the throne of Monaco.
Prince Albert is the son of Princess Grace and Prince Rainier III.