The isolation experience, which will last a year starting on Friday, will be the longest of its type attempted.
Experts estimate that a human mission to the Red Planet could take between one and three years.
The six-strong team will live in close quarters under the dome, without fresh air, fresh food or privacy.
They closed themselves away at 15:00 local time on Friday (01:00 GMT Saturday).
A journey outside the dome – which measures only 36ft (11m) in diameter and is 20ft (6m) tall – will require a spacesuit.
A French astrobiologist, a German physicist and four Americans – a pilot, an architect, a journalist and a soil scientist – make up the Nasa team.