The veteran TV personality's last day co-hosting the popular morning talk show will be November 18. The news came as "LIVE!" began its 24th season in national syndication.
The show will continue with Kelly Ripa, who joined Philbin as co-host a decade ago. However, no new co-host has yet been chosen to team up with Ripa.
Philbin, 80, announced last January that he planned to leave the show by year's end, but didn't specify a date.
Philbin has been a fixture in broadcasting for decades. He got his start in the 1960s as regular sidekick for host Joey Bishop. He then worked in Los Angeles at ABC7 during the 1970s, both as an entertainment reporter and as the host of "A.M. Los Angeles."
But New York City beckoned and Philbin took his talk show skills to his hometown. The show went national in 1988 with his co-host, Kathie Lee Gifford.
Gifford left the show in 2000 and was replaced by Ripa.
The three-time Emmy Award winner was honored with a Lifetime Achievement Award from the National Academy of Television Arts & Sciences at the Daytime Emmy Awards in 2008. The broadcasting legend was also awarded a star on the Hollywood Walk of Fame in 2003.
In recent years, Philbin has dealt with some major health issues. He underwent triple bypass surgery in 2007 and a hip replacement in 2009.
"LIVE! With Regis and Kelly" airs at 9 a.m. PT on ABC7.
The Associated Press contributed to this report.