Doyle grew up in Brooklyn, New York, raised as the eldest son of a police officer and a housewife. He spent the first six months of his life in an orphanage before being adopted. He graduated from Pope John XXIII Regional High School in Sparta, New Jersey, in 1974, where he played varsity football and basketball. In 1978, Doyle earned a Bachelor of Science Degree in Aeronautics from Embry-Riddle Aeronautical University, while also receiving his FLIGHT training.

Previously a corporate jet pilot and after a decade as a stockbroker on Wall Street, Doyle made an abrupt career change into acting in 1991, when he moved to Los Angeles. His first television role was on the series Moonlighting where he played a potential replacement for Bruce Willis' character. This was followed by a recurring role as a Lawyer on the soap opera The Bold and the Beautiful. Babylon 5 was his first significant starring role, starring as security officer Michael Garibaldi. Doyle quipped that on Babylon 5 he was a "Mick from Brooklyn playing a Wop from Mars."

Doyle was married to his Babylon 5 co-star Andrea Thompson from 1995 to 1997. They were married in Cabo San Lucas, in Baja California Sur, in a short ceremony. Doyle remarked that "If the ceremony takes longer than it takes for a Margarita to separate, it's too long".

From 1996 to 1997 Doyle was the voice of the title character in animated cartoon Captain Simian & the Space Monkeys.

Following his work on Babylon 5, Doyle ran as the Republican Party candidate for a seat in the U.S. House of Representatives in 2000. During the primary, Doyle did not spend any money on the campaign, and received 43,000 votes, less than half as many as the Victor, incumbent Brad Sherman. He lost the general election on November 7, 2000 with Sherman earning 66% of the vote to Doyle's 30%, the Libertarian candidate's 3%, and the Natural Law candidate's 1%. In December 2011, Doyle endorsed Ron Paul for the Presidency of the United States.

Doyle was announced as the replacement program for The Savage Nation in Talk Radio Network's lineup in October 2012. The Savage Nation, at the time the third most-listened-to radio talk show in the United States, abruptly ended its run September 26 when host Michael Savage won a lawsuit against TRN. Doyle replaced Savage on all of Savage's approximately 300 affiliates except for those who chose their own replacement programs. He launched the new media content platform EpicTimes in February 2013, which served as a "one stop shop" for both hard hitting news of the day as well as entertaining "water cooler" type pieces. It was subsequently banned within China.

Weekdays from 3 p.m.–6 p.m. PT (6 –9  ET), the Jerry Doyle Show aired on the Talk Radio Network, although the show aired at different times in different markets. It was the sixth most popular talk radio show in the country, with an average of 3.75 million listeners on a weekly basis by early 2012.

On July 27, 2016, eleven days after his 60th birthday, Doyle was found unresponsive in his Las Vegas home, and declared dead shortly thereafter. Condolences were received from his former co-stars, including from Bruce Boxleitner, who wrote that he was "so devastated at the news of the untimely death of my good friend". Babylon 5 creator J. Michael Straczynski released a statement, saying "Regardless of whatever was going on in his life, whether it was marital issues, a broken arm, forced couch-surfing with Bruce and Andreas or other problems, he never once pulled a prima donna on us; he showed up every day on time, knew his lines, and insisted that the guest cast live up to the standards of the main cast." The Clark County Coroner's Office later stated that Doyle died from natural causes, with complications from chronic alcoholism being a contributing factor.