Born and raised in Florida, McCollum attended the University of Florida, where he was inducted into the University of Florida Hall of Fame (the most prestigious honor a student leader could receive at UF), and served as president of Florida Blue Key. McCollum began his professional career in the United States Navy's Judge Advocate General Corps from 1969 to 1972. In 1973 McCollum entered private practice in Orlando, and immediately became involved in local politics, serving as Chairman of the Seminole County Republican Party from 1976-1980. In 1980 McCollum was elected to the U.S. House of Representatives from a district including Walt Disney World and most of Orlando.

McCollum gained national attention in 1998-1999 as one of the House Managers of President Bill Clinton's impeachment trial, and in 2000 launched an unsuccessful bid for the seat of retiring Republican Senator Connie Mack, narrowly losing to former Congressman Bill Nelson.

McCollum made his second run for the Senate in the U.S. Senate election, 2004. During the early months of 2004, he competed with former Bush administration official Mel Martinez for the position of Republican front-runner: by mid-summer, businessman Doug Gallagher began approaching McCollum and Martinez in support as well. McCollum stressed his own experience on homeland security issues, and contrasted his position on tort reform against Martinez's background as a plaintiff's lawyer. Inexplicably, McCollum, who was considered one of the most conservative members of Congress for many years, was lambasted by Martinez as "the darling of homosexual extremists" due to his one-time vote in favor of gay hate crimes legislation. Connie Mack appeared with McCollum at a press conference to denounce Martinez's bigotry, but Martinez went on to win the primary on August 31 by a wide margin, defeating McCollum in most parts of Florida with the exception of the Tampa Bay area. After days of feet-dragging, McCollum endorsed Martinez for the general election.