"He will be undergoing a routine heart operation to correct genetically defective valves," the organisation said in a statement on Thursday.
"The operation has been planned for some months and has been timed to minimise the impact on the running and decision making capability of the Premier League."
Scudamore, 54, has been in charge of the Premier League for 15 years and has overseen a huge increase in the value of its television rights at home and abroad.
That money has helped to make the English top flight the most lucrative league in the world.
Scudamore was forced to apologise last month after a Sunday newspaper published details of sexist email exchanges between him and a friend. Critics had called for him to be sacked.
He is expected to be back in his office at the end of July, the Premier League said. The new season begins on Aug. 16.
(Writing by Keith Weir, editing by Tony Jimenez)
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