Wagner also won the Missouri junior college championship in 1980, and at one point considered a career in pro golf. He has a Celebrity Golf Classic named after him that raises funds for the Leukemia & Lymphoma Society. Wagner created the event to support the Society's mission to cure such cancers as leukemia, lymphoma, Hodgkin's disease, and myeloma, and to improve the quality of life of patients and their families. The Golf Classic raised more than $600,000 in its first two years to fund critical cancer research and patient services.

Wagner first appeared on the scene in 1982 in the role of Clint Masterson, in Douglas Marland's short-lived cable soap opera, A New Day In Eden (co-produced by Susan Flannery, who would later be Wagner's co-star on The Bold and the Beautiful).

Although Wagner had been playing the guitar since he was 14, his initial audition for the role of "Frisco Jones" on General Hospital with Producer Gloria Monty did not include any singing. Wagner had five auditions with ABC before ultimately winning the role of "Frisco Jones". His final audition in 1983 included performing the Kenny Loggins song "Wait a Little While." ABC musical honcho Kelli Ross hooked Wagner up with her good friend in legendary Producer Quincy Jones who oversaw his initial 5 song EP "All I Need". Eventually, they would release a full ten song LP of "All I Need" once the song "All I Need" began to rise the charts. Quincy Jones protégés Glen Ballard and Clif Magness produced Wagner's first two albums on Qwest Records/Warner Brothers. Wagner's singing talents led him to appearances on American Bandstand, Solid Gold, Soul Train and The Merv Griffin Show.

While he toured as a rock/pop performer in concert consistently from 1985–1988, Wagner did not perform in the 1990s except for an occasional benefit appearance. In 2005, Wagner resumed performing in concert sporadically. His more recent concerts have included a diverse blend of songs from his own catalog, cover songs from artists such as Neil Young, Lindsey Buckingham, and Paul McCartney, and originals.

Eventually, his musical theater talent led to the title role(s) in a Broadway run of Jekyll & Hyde, making him the first Celebrity casting. Wagner has stated this was "a role of a lifetime" and performing the dual characters on Broadway was his most fulfilling professional experience. Wagner says "the role I had the most fun playing, TV-wise, would be Dr. Peter Burns (Melrose Place). He was sort of an evil character who could redeem himself. Theatrically, it was when I played Dr. Jekyll and Mr. Hyde in Jekyll & Hyde on Broadway." He also appeared in a national theatre tour in 1987 in the role of Tony in West Side Story, and a national tour of Grease in 1988.

He also played Warren Lockridge on Santa Barbara from 1991 until that series' conclusion in 1993.

He appeared for many years on Aaron Spelling's Fox nighttime soap opera Melrose Place, as the alternately caring/conniving Dr. Peter Burns (1994–99); he directed episodes as well. His character and Heather Locklear's "Amanda" were featured together on a beach in the series finale's closing scene, having faked their own deaths.

He appeared in another Aaron Spelling project, the NBC television series Titans with Yasmine Bleeth in 2000, and in Spelling's daytime soap opera Sunset Beach in 1997.

From 2003-2012, he played Nick Marone on the CBS daytime soap The Bold and the Beautiful.

Wagner is an avid Golfer and is ranked as one of the leading Celebrity golfers. He is the only non-professional athlete to have won the American Century Celebrity Golf Classic, the annual competition to determine the best golfers among American Sports and entertainment celebrities. Wagner first won the event in 2006 and repeated as champion in 2011, when he bested Dallas Cowboys quarterback Tony Romo. He has a total of nineteen top ten finishes. The tournament, televised by NBC in July, is played at Edgewood Tahoe Golf Course in Lake Tahoe.

The Wagners have two sons, Peter (born 1990) and Harrison (born 1994). Wagner began dating his Melrose Place love interest Heather Locklear in 2007; they became engaged in August 2011. The couple called off their engagement on November 15, 2011.

In November 2011, Jack met his 23-year-old daughter, Kerry, for the first time at a concert in Florida. Kerry had been placed for adoption at birth by her birth mother and had recently hired a private investigator to find both of her biological parents. This was the subject of Wagner's "personal story" in his Dancing with the Stars performance on April 2, 2012.

In May 2013, Wagner confirmed to Soaps In Depth that he and his former The Bold and the Beautiful co-star Ashley Jones had been dating for about a year. They are no longer together as of 2015.

In 2014, Wagner released the full-length release "On the Porch". A notable song from this release was the fan-favorite "The Right Key", which made its debut on General Hospital in 1989. He made a music video for "Driving Miss Daisy" which premiered on YouTube.