The Mercury Messenger is due to launch after 0700 GMT on Monday from Cape Canaveral in Florida for a seven-year journey.
After travelling eight billion kilometres, the spacecraft will slip into orbit around the solar system's innermost planet in 2011.
Messenger will then gather information on the composition and structure of the planet's crust, its geological history, polar regions, atmosphere and magnetic environment as well as the make-up of its core.
Mission scientists hope the $427m mission will help solve some of the mysteries surrounding one of the least studied planets in the solar system.
What is known for sure is that Mercury is about two-thirds iron and is the only other planet to have a global magnetic filed.
Most of what scientists know about Mercury comes from the Mariner 10 spacecraft, which flew by it three times in 1974 and 1975.
However, that probe gathered detailed data on less than half of the planet's surface.