Dozens of other acts will perform through Monday at Big Four Station Park.
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The free entertainment runs each night of the ten-day fair from August 17-27.
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Blessings in a Backpack is the primary beneficiary of the gala this year.
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Danny Wimmer Presents said more than 170,000 attended Louder Than Life last year.
The Metallica Scholars Initiative was established in 2019.
My Morning Jacket planned to play at Iroquois Amphitheater on June 24 and at Waterfront Park on June 25, the band's first live dates in Louisville in six years.
Country star Trace Adkins, the Oak Ridge Boys and Russell Dickerson are also part of this year's concert lineup.
If you already have a ticket for that Rupp Arena show from the previously canceled concert, it will be honored during the new date.
The festival will be held at the Kentucky Exposition Center for four nights, starting Thursday.
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In announcing the rocker's breakthrough case, Kiss has also revealed that the entire band and touring crew are fully vaccinated.