The comedian says he is donating all the proceeds from Friday's show at the Tennessee Performing Arts Center, just a few blocks from the scene of widespread flood damage.
The proceeds will be split between the Community Foundation of Middle Tennessee and American Red Cross Disaster Relief Fund.
"This is a tough time for a great city, and I'm very happy to donate the proceeds from this show to the local organizations that are bringing help where it's needed," Seinfeld said in an e-mail to The Associated Press.
Seinfeld is one of dozens of stars and organizations who have offered help after a deadly string of storms caused widespread flooding in Tennessee. Thousands of homes were damaged or destroyed and more than 34 people died across three states, including 22 in Tennessee.
A telethon featuring Brad Paisley and Lady Antebellum will be held Sunday night on cable network GAC. A local telethon the week after the floods hosted by Vince Gill raised more than $1.7 million.
Taylor Swift has donated $500,000 to relief organizations and will continue to help raise funds by appearing in "Nashville Rising," a June 22 benefit concert hosted by Faith Hill and Tim McGraw. The lineup includes Carrie Underwood, Miley Cyrus, Brooks&Dunn, Miranda Lambert, Martina McBride and many others.
Ke$ha, a Nashville-area native, has a benefit concert planned for June 16.
And the Country Throwdown Tour will take the effort on the road this summer. Some artists on the traveling tour, including Montgomery Gentry, Eric Church and Jack Ingram, will donate a portion of their merchandise proceeds to flood relief. Organizers also are giving 50 cents from every ticket to charity with a percentage going to Hands On Nashville.