Regis Philbin first talk show, The Regis Philbin Show, on KGTV-TV in San Diego, spawned his now well-known style of host chat that has become his trademark. This led to an Emmy- winning Los Angeles show called Philbin's People in which Philbin and popular personalities discussed current issues.

In 1983, he joined Cindy Garvey on New York City's "The Morning Show", but the show did not fare well in the ratings until Garvey was replaced by Kathie Lee Gifford in 1985. The show was renamed "Live! With Regis & Kathie Lee" when it became nationally syndicated in 1988. Philbin has been nominated for an Emmy seven times for his co-hosting role.

Philbin wrote his memoirs "I'm Only One Man" in 1995, and has co-authored "Entertaining with Regis and Kathie Lee" and "Cooking with Regis and Kathie Lee".

In 1999, Philbin created new material for his memoirs, when he co-hosted the highest-rated prime-time game show in history, the U.K. import "Who Wants to be a Millionaire". In February 2000, Philbin reportedly inked a deal with ABC's corporate owner Disney that will bring his annual salary for "Who Wants to be a Millionaire" to an unprecedented $20 million.