He served on the city council of Hialeah, Florida from 1987 to 1990. In 1990, he became the youngest county commissioner in Dade County's history. On October 1, 1996, Penelas became the first mayor of Miami-Dade County, after the Dade County and City of Miami governments were merged.
In 1999, People Magazine named Penelas "America's sexiest politician."
Unlike most Cuban-American leaders in Florida, Penelas is a member of the Democratic Party. During the Elián González controversy in 2000, Penelas defied the wishes of the Clinton administration by refusing to cooperate with federal authorities in the repatriation of the Cuban boy. Later, during the 2000 presidential race, Penelas refused to campaign alongside Al Gore, and made no comments during the controversy over Miami-Dade County's ballots in the aftermath of the election. This led many Democrats to criticize Penelas as a Republican turncoat, although he has since apologized for his actions.
If elected, Penelas would be the only Hispanic senator.