Of Ukrainian descent, Palance was born in Lattimer Mines, Pennsylvania. In the late 1930s he started a professional boxing career. Fighting under the name Jack Brazzo, Palance reportedly compiled a record of 15 consecutive victories with 12 knockouts before losing a decision to future heavyweight contender Joe Baksi. During World War II, Palance, a B-24 bomber pilot in training, crashed during a training flight and received severe burns that led to extensive facial surgery, resulting in his gaunt, pinched face.

In 1947, Palance made his broadway debut, followed three years later by his first screen performance in the movie Panic in the Streets (1950). He was quickly recognized for his skill as a character actor, receiving an Academy Award nomination for only his third movie role, as Lester Blaine in Sudden Fear. The following year, he was nominated again, this time for his role as the evil gunfighter Wilson in Shane. Several other Western roles would follow, but he would also play Dr. Jekyll and Mr. Hyde, Dracula and Attila the Hun. In 1957, Palance won the Emmy Award for Best Actor for his portrayal of Mountain McClintock in the Playhouse 90 production of Rod Serling's Requiem for a Heavyweight.

In the 1980s, Palance, along with his daughter Holly, hosted the Ripley's Believe It or Not! television series.

He won an Academy Award for Best Supporting Actor in 1991 for City Slickers. Stepping to the microphone to accept the award, he looked at Billy Crystal, the host of the awards program and his co-star in the movie, and said, "Billy Crystal ... I crap bigger than him." He then dropped to the floor and demonstrated his ability, at age 73, to perform one-handed push-ups. Crystal turned it into a running gag as at various points in the broadcast he announced that Palance was backstage on the Stairmaster; had bungie-jumped from the Hollywood sign; rendezvoused with the space shuttle in orbit; fathered all the children in a production number; been named "People" magazine's Sexiest Man Alive; and won the New York primary election. At the end of the broadcast, Crystal told everyone he'd like to see them again "but I've just been informed Jack Palance will be hosting next year." The following year, host Crystal arrived on stage atop a giant model of the Oscar statuette, towed by Palance.

For his contribution to the television industry, Jack Palance has a star on the Hollywood Walk of Fame at 6608 Hollywood Boulevard (which was once in front of the display window of Frederick's of Hollywood). In 1992, he was inducted into the Western Performers Hall of Fame at the National Cowboy & Western Heritage Museum in Oklahoma City, Oklahoma.

He currently resides in Tehachapi, California in retirement.