Lyons was born in New York City, one of the four sons of Sylvia and Leonard Lyons. His godfather was the playwright Sidney Kingsley and his godmother was the actress Madge Evans.

Lyons was the film critic for WPIX from 1970 to 1991, and a co-host of the movie review show Sneak Previews from 1982 to its demise in 1996. On American AM radio, he hosted a show, "The Lyons Den", on WCBS from 1975 to 1993. The title "The Lyons Den" is taken from the New York Post column that his father wrote for 40 years. He joined WNBC in 1996 as the station's film and theatre critic. His last report on WNBC was on June 26, 2009. He reported during Live at Five and NewsChannel 4 newscasts. Lyons co-hosted the syndicated movie review TV show Lyons & Bailes Reel Talk for several years with fellow film critic Alison Bailes (which was also canceled following his departure from WNBC). After leaving WNBC, he has said that he will continue to host a syndicated radio program called "LYONS DEN RADIO". In addition to his work as a critic, he has appeared as himself in The French Connection, Deathtrap, and the TV series Wiseguy.

Lyons is the author of four books, including Jeffrey Lyons' 101 Great Movies for Kids. He and his brother Douglas have written several baseball trivia books, Out of Left Field, Short Hops and Foul Tips and Curveballs and Screwballs. A fourth in the series has been completed. Jeffrey and Douglas Lyons have lectured at the Smithsonian Institution and at the National Baseball Hall of Fame and Museum in Cooperstown, New York. Lyons has been a guest announcer, both as play-by-play and analyst, for the Boston Red Sox radio network and Red Sox games in Spanish.

Lyons has received two honorary degrees, from Hofstra University in 2000 and St. Mary's College in 2002. He also holds a Juris Doctor degree from Syracuse Law School. Lyons' son is the television personality and movie critic Ben Lyons, who also uses the name "The Lyons Den" in his own work as a critic on the E! Channel's "Daily 10" show, co-hosting "At The Movies" and on "Good Morning, America."