The latter show followed the Hot Talk format, which brought Leykis much success. Due to the nature of the show, Leykis has been described as a shock jock by many. The show's best-known feature was "Leykis 101," in which he purported to teach men "how to get laid" while expending the least amount of time, money, and effort.

Tom Leykis was born August 1, 1956, at a time when his parents, Harry and Laura (née O'Mara), lived in the Bronx. Leykis spent his early childhood at 1504 Sheridan Avenue, Apartment 3H, in The Bronx, New York City, New York and he has two sisters, Laura and Sarah, and a brother, Harry. His father was a union leader at The New York Post. At a point in Leykis' childhood, he moved with his family to Selden, Long Island, where he completed high school and graduated at 16 from Newfield High School. He then moved away from the family home to study broadcasting at Fordham University but dropped out due to a lack of finances.

Leykis began his radio career in the state of New York. At the age of 14, he was once a fill-in host for WBAB later working in 1979 for Mark Simone's WPIX talk show comedy titled The Simone Phone where he was featured as the host's sidekick. Leykis eventually left WPIX, later went to WBAI leaving in the fall of 1981 to go to Albany to work at WQBK-AM. Leykis also contributed to a show called The Phonebooth in WABC that ended in 1981. After his departure from WABC, Leykis was offered a full-time radio hosting job in Staunton, Virginia.

On Monday, February 27, 1984, the Tom Leykis Show aired on WNWS in Miami to replace the WNWS night show hosted by talk radio personality Neil Rogers. Rogers, who had previously signed conflicting employment contracts with both WNWS (790 AM) and WINZ (940 AM), had just won permission from a Miami court to take his act to WINZ and hoped leaving WNWS would be devastating to Leykis' program. Rogers and Leykis became rivals and, in June 1984, just after Denver radio talk show host Alan Berg was assassinated, Leykis told listeners Neil Rogers' real name and urged callers to harass his on-air rival. By January 1985, Leykis had the top-ranking evening talk show in the market. In September 1985, Leykis abruptly left his WNWS job over concern about the pending WNWS-WGBS merger and began work at Phoenix's KFYI-AM.

As program director at KFYI, Leykis constructed a politically well-rounded host lineup inserting himself as a "left leaning libertarian" in the afternoons. Leykis was known for his method of gathering new callers for the station by provoking rival station KTAR. In 1987, Leykis abruptly left KFYI because of differences with station management that still have a shroud of secrecy surrounding the details. To this day, KFYI hosts are prohibited from discussing the details of Leykis' departure from the station. While still in Phoenix, Leykis also had a local cable television show called Backstage Pass.

After leaving Phoenix, Leykis moved on to Los Angeles to work for KFI, where he hosted a talk-radio program from 1988 to 1992, as a liberal counterpart to Rush Limbaugh. During this time, KFI was hit with a $6,000 Federal Communications Commission (FCC) indecency fine over Leykis' on-air comments, however, the fine was paid in full from contributions by listeners. During Leykis' tenure at KFI, KFI host Geoff Edwards was suspended and then resigned over an incident related to steamrolling a massive collection of Cat Stevens' work sent in by listeners, which was motivated by Leykis' denouncement of Cat Stevens' comments about Salman Rushdie. A local Nazi historian likened the stunt as being reminiscent of a Nazi book burning.

On September 29, 1992, KFI management dismissed Leykis with only an hour's notice, based on what Leykis claims they called "a business decision"; KFI assumed the obligation of pay him his contracted salary, estimated at $400,000 per year, for the remaining six months of his contract.

Leykis next moved on to Boston and WRKO. He later left the Boston for a new job in Los Angeles after a publicized domestic disturbance with then-wife Susan at the end of 1993. In March 1994, pretrial probation was granted and the charges stemming from that assault were dropped in exchange for his attendance in a program for batterers.

In 1994, Leykis began the infamous, nationally syndicated program, The Tom Leykis Show on Westwood One from Culver City, California. The final years of the show were produced from Paramount Pictures studios in Hollywood.

Leykis' started the Internet radio station New Normal Music in July 2010.