McDonald was born in Atlanta, Georgia and he graduated from Davidson College. He was a urologist and President of the John Birch Society, an ultra-conservative conspiracist organization.

McDonald was elected to the House in 1974 as a member of the Democratic Party. Some feel that McDonald's ultra-conservative views limited his influence in Washington. McDonald is also noted for using amendments to stop government aid to homosexuals. During his terms in Congress, McDonald founded the Western Goals Foundation which was intended to combat the threat from Communism and he was sued for malpractice for using Laetrile to treat a patient's cancer.

On September 1, 1983, he died when Korean Air Flight KAL-007 was shot down by Soviet fighters, apparently becoming the only congressman ever killed by the Soviets during the Cold War. The portion of interstate highway 75 which runs through the congressional district he represented is named in his honor.

Some people, including ex-U.S. Senator Jesse Helms, R-North Carolina, have said they believed that all or most of the passengers and crew of flight KAL 007 survived after their damaged aircraft managed to land safely at an airfield on Sakhalin island, and were then placed inside various Soviet "gulag"-style slave labor camps, prisons, and orphanages, in the case of the many children. This theory was largely discredited when the flight recorders that the Soviets had recovered were released to the public after the Soviet Union fell.

After McDonald's death, a special election was held to fill his seat in Congress. McDonald's widow, Kathy, was a candidate, but she lost to George "Buddy" Darden. Much of the congressional district McDonald represented would later be represented by Newt Gingrich.