Smith began his broadcasting career at Denver radio stations KHOW and KIMN and Cincinnati radio station WLW (1973—81). From 1981-82, he worked for Denver's public television station, KRMA-TV. From 1982-85, he served as a reporter and anchor for KMGH-TV, the CBS affiliate in Denver. In 1986, Smith joined CBS News as a reporter and was named a correspondent in 1987.

For 13 years, Smith was a contributor to The CBS Evening News with Dan Rather, 48 Hours, and CBS News documentaries. From 1987-96, he served as a co-anchor for the CBS morning show CBS This Morning. In 2002, Smith returned to the CBS morning show, renamed The Early Show.

In addition to his TV assignments, Smith does the daily "Harry Smith Reporting" editorial for the CBS Radio Network. He was host of Biography until 2003.

Smith received his B.A. degree in Communications and Theater from Central College in Pella, Iowa.

Smith lives in New York City with his wife, sportscaster Andrea Joyce, and their two sons.

Smith is a cyclist. He regularly commutes on a folding bike to the CBS studios in New York and he also rides a "racing" road bicycle.