Thousands will celebrate Independence Day at the Folds of Honor FreedomFest.
The festival will also have an impact on traffic most of the day.
Organizers said venues will be set up at Veterans Park and River West Festival Park, so the closures will be in those areas.
Boulder between 18th and 21st streets will close at 10:00 Wednesday morning, along with 21st Street between Boulder and Boston.
The 23rd Street bridge between Boulder and Jackson will also shut down at 10 a.m.
On the east side of the river, Riverside between Denver and 21st will close at 5 p.m., then southbound on Riverside from Southwest Boulevard to Denver will close for the fireworks at 9:30 p.m.
On the west bank, Jackson will close between 20th and 23rd streets at 4 p.m.
There will also be parking lane closures along Cincinnati and Boston near the festival.
FreedomFest organizers said the areas will reopen after the fireworks show.