DeGeneres, 63, will discuss the decision on Thursday's show with guest Oprah Winfrey.
"When you're a creative person, you constantly need to be challenged and as great as this show is, and as fun as it is, it's just not a challenge anymore," DeGeneres said.
The Ellen DeGeneres Show debuted in 2003 and has won more than 60 Emmy awards. It is produced by AT&T Inc's Warner Bros and syndicated to TV stations.
DeGeneres started her career in stand-up comedy in her New Orleans hometown before moving to television, where she starred in comedy series "Ellen" in the mid-1990s.
In 1997, both she and her TV character came out as homosexual long before being gay was accepted in mainstream America. "Ellen" was canceled a year later, but DeGeneres returned to television in 2003 with her daytime show.
An advocate for animals, gay rights and anti-bullying campaigns, DeGeneres became known for promoting kindness and compassion on her light-hearted show
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