Born as Patrick Alan Lilley in Inglewood, California in 1953, Patrick began his acting career in 1961 at the age of 8. He made his feature-film debut in the 20th Century Fox comedy–fantasy The Two Little Bears. Over the next two years, Patrick went on to appear in guest-starring roles on numerous television series, including Ben Casey, Alcoa Premiere, Bonanza, My Favorite Martian, Mister Ed, and Rawhide and recurring roles on The Real McCoys and General Hospital. When recounting how he began his acting career, Patrick explained "I owe my career to my sister. She was the one who got me started and gave me all the encouragement. She always wanted to be an Actress and was on the casting call sheet one day. She was asked if there were any other children at home. She told them about me, and I got some small roles, then some bigger ones..."

After The Munsters ended, Patrick continued to appear in guest-starring roles on various popular television series of the 1960s, including I Dream of Jeannie, Death Valley Days, Gunsmoke, The Monkees, Daniel Boone, and Adam-12, as well as a recurring role as Gordon Dearing on the CBS family comedy series My Three Sons. During this time, Patrick also appeared in several Walt Disney films, including Way Down Cellar, The Young Loner and The One and Only, Genuine, Original Family Band, as well as portraying the role of Milo in the 1970 MGM live-action/animated film The Phantom Tollbooth.

When asked how he landed the role of Eddie, Patrick recalled "I had a lot of experience. But maybe it was because my fangs were my own teeth. My teeth were so bad, that even when I closed my mouth they stuck out. I was about a head smaller than the other kids, and they liked that because it played off Herman's height." Living on the East Coast at the time, Patrick commuted to Los Angeles every week during filming of the series, appearing in 70 episodes during The Munsters two-season run from 1964 to 1966.

In 1971, Patrick landed the starring role on Sid and Marty Krofft's Saturday morning children's program Lidsville, broadcast on ABC. In the psychedelic fantasy series, Patrick portrayed Mark, a boy lost in a strange land of walking, talking, singing hats, opposite veteran character actors Charles Nelson Reilly and Billie Hayes. The show was in production from 1971 to 1973.

In 1975, Patrick left acting to work for his father and began to learn to play the bass. In 1983, he recorded the song, "Whatever Happened To Eddie?" (b/w "Little Monsters"), with several instrumentalists and backup Singers under the group name "Eddie and the Monsters." Set to the tune of the Munsters theme, the song details his life as a Munster. ("You might wonder why I have a dragon for a pet – Well he's just there to keep me company on the set.") He recorded a second single, "It's Only Halloween", which was released on Park Lane Drive Records in 2007.

In 2002, Patrick co-hosted Macabre Theatre with Natalie Popovich aka “Ivonna Cadaver.”

In addition to his music, Patrick returned to occasional film and television work, including making cameo appearances as "Himself" on episodes of the Fox animated television series The Simpsons and the 2003 comedy film Dickie Roberts: Former Child Star, as well as appearing as a grown-up Eddie Munster in a Little Caesars Pizza commercial.

Patrick made a cameo appearance in the 2005 retro-horror film Frankenstein vs. the Creature from Blood Cove, directed by william Winckler, playing a man who had become a werewolf, speaking a line of dialogue in comical reference to The Munsters.

He also responded in a April 2017 interview with ComingSoon.net, where the Director had ever recalled if his TV mother (Yvonne DeCarlo) was hiding tiny portions of dialogue, around the set, attaching to props to help jog her memory, where it was added to her performance: "No, not in The Munsters she wasn’t doing that. Maybe later in life. Because sometimes your memory starts slipping on you. But that’s a great idea, actually! I’ll have to remember that!" He also had said if he had ever kept in touch with his on-screen family, after The Munsters was canceled, esp. DeCarlo, herself, who passed away on January 8, 2007, was: "No, after the show ended, everyone went their own ways. But in the early ’80s, I contacted Al Lewis and we became friends and I started attaching myself to the Munster name and brand. And then 10 years after that I started talking to Yvonne. I was actually a guest on The Vicki Lawrence Show where I was this surprise guest brought out for Yvonne and after that we became friends. I started going up and visiting her and she was somewhat of a recluse, living in North Los Angeles and I introduced her to this guy in Hollywood who would send her care packages, movies to watch and sort of get her back in the loop of Hollywood."

Patrick moved to Philadelphia for McCall, but the pair broke up just after Halloween in 2010, according to Patrick's agent. The following week, on November 11, 2010, People and E! Online reported that Patrick had entered a drug rehabilitation facility in New Jersey.

In May 2011 Patrick announced that he had been diagnosed with prostate cancer. He said that the disease was detected early and he claimed to be positive about the prognosis — "If you catch it early, there's a good chance of survival. I'm told I have a 90 percent chance of recovery and of living another 20 years." In an interview with US Celebrity tabloid magazine Star, he said "I went 41 years trying to kill myself. And then finally got to the point when I want to live I was diagnosed with prostate cancer. My first thought when I was told this was 'Isn't this a kicker?' I get clean, my life is together, and now God is going to punch my ticket."