The white Atlas V 401 rocket carrying the Mars Atmosphere and Volatile EvolutioN (MAVEN) orbiter blasted off on schedule at 1:28 pm (2358 IST).
"Everything is looking good," said NASA mission control.
The flawless liftoff of the USD 671 million spacecraft kicked off the 10-month journey to the Red Planet.
Arrival at Mars is scheduled for September 2014, with the science mission of the solar-wing paneled orbiter set to begin two months later.
Much of MAVEN's year-long mission will be spent circling the planet 6,000 kilometers above the surface.
However, it will execute five deep dips to a distance of just 125 kilometers above the Martian landscape to get readings of the atmosphere at various levels.
Researchers have described the mission as a search for a missing piece to the puzzle of what happened to Mars' atmosphere, perhaps billions of years ago, to transform Earth's neighbour from a water-bearing planet that might have been favourable for life to a dry, barren desert.
"The spacecraft will investigate how the loss of Mars' atmosphere to space determined the history of water on the surface."
One of its three scientific tools is a solar wind and ionosphere gauge called the Particles and Fields Package, built by the University of California at Berkeley Space Sciences Laboratory.
A second tool, called the Remote Sensing Package, was built by the Laboratory for Atmospheric and Space Physics at the University of Colorado and will determine global characteristics of the upper atmosphere and ionosphere.
"With MAVEN, we're exploring the single biggest unexplored piece of Mars so far," said the mission's principal investigator, Bruce Jakosky.
NASA has sent a series of rovers to explore the surface of the Red Planet, including its latest, Curiosity, which arrived last year.
The deep space orbiter launched earlier this month by India seeks to find traces of methane from Mars and may arrive two days later than the US spacecraft.
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