Bruce Cantrell, 63, and Jessica Fain, 25, will spend more than two months at a depth of 7.6 metres, to raise awareness about ocean issues.
"When we talk about it and you think about it, 72 days seems like a long time," Mr Cantrell said.
"But when you look at everything that's going to be scheduled I think it's going to go by a little faster than we think."
The project, which is called the 'Classroom under the sea', will see the two educators hosting weekly online video classes and interviews from marine science experts.
Former astronaut, Buzz Aldrin, plans to dive down to the lab to join the pair for an interview session.
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The duo are living in the world's only underwater hotel in Florida, which will also double as their lab.
"As far as the habitat itself, we're going to have to work together as dive partners. We're going to have to go out into the lagoon, clean the windows, do the vacuum systems for the algae," Ms Fain said.
"We're going to have a lot of maintenance stuff we'll have to do and work really well as a team."
The current record holder, Richard Presley, spent 69 days underwater at the same underwater venue in 1992.
