Zilisch grew up in Mooresville, North Carolina, and began competing in go-karts at the age of five. He spent a decade in the discipline, racing domestically before venturing to Europe, where he competed in the FIA OKJ World Championship class in 2018–2020 and made the A final in both 2019 and 2020. In 2017 he won the Mini Rok World Championship in South Garda, Italy, defeating more than 160 competitors from 33 countries. His biggest karting achievement came in 2020 when he became the first American ever to win the CIK-FIA Karting Academy Trophy, a three-race series run on identical equipment for drivers from around the world.
His mother, Janice Kerr, was a gymnast on the Canadian women's national artistic gymnastics team and a member of the 1983 World Artistic Gymnastics Championships squad. She was the NCAA Southeast Region all-around champion in 1987 and 1988.
Zilisch transitioned to cars in 2021 with the Sports Car Club of America in Spec Miata, immediately setting three track records and reaching the podium multiple times before finishing third at the SCCA Run-offs in Indianapolis. He won the Mazda MX-5 Cup Shootout scholarship that year, earning $110,000 to compete in the series in 2022.
In the 2022 Mazda MX-5 Cup he recorded four wins and narrowly missed the championship at Road Atlanta after a post-race penalty to a rival reshuffled the order. He was simultaneously competing in the Trans-Am TA2 Series for Silver Hare Racing, where a debut at Virginia International Raceway had already seen him claim pole and shatter the track record. He also ran Pro Late Models and Late Model Stock Cars, scoring wins at Hickory Motor Speedway.
In 2023, Zilisch made his ARCA Menards Series debut at Watkins Glen for Pinnacle Racing Group, qualifying second and dominating the race before being moved out of the lead on the final corner, finishing second with a broken front sway bar.
Signed by Trackhouse Racing as a developmental driver in January 2024, Zilisch began the year racing in ARCA, the Craftsman Truck Series, the Xfinity Series, and IMSA simultaneously. In ARCA Menards Series East he won five consecutive races on intermediate and short tracks, going four-for-four after his opening-round difficulty.
On the endurance front, he co-drove an LMP2 entry at the 24 Hours of Daytona and won the LMP2 class on his first attempt, then repeated the feat at the 12 Hours of Sebring later in the same season — a remarkable double on debut starts in both events.
His NASCAR breakthrough arrived at Watkins Glen in the Xfinity Series: starting from pole, he led the most laps and managed fuel through two overtime restarts to win on his series debut, becoming the first driver in more than three years to win in their Xfinity debut, just weeks after turning eighteen.
Zilisch ran full-time in the Xfinity Series for JR Motorsports in the No. 88 car. Despite a slow start — including finishes outside the top 25 at Daytona and Atlanta — he broke through at Circuit of the Americas and embarked on a dominant mid-season stretch. He won at Pocono, Sonoma, Dover, Indianapolis, Watkins Glen, Portland, and Gateway, among others, accumulating ten victories across the season.
The Watkins Glen celebration turned dramatic when Zilisch lost his footing exiting the car after the victory and fell from the window sill, suffering a broken collarbone. He attempted the next race at Daytona, but had to hand the car to Parker Kligerman at the first caution due to the injury. Kligerman won the race while Zilisch received credit as the starting driver.
He also suffered a back injury at Talladega after being spun from the lead, which forced him to sit out the Texas race, where Kyle Larson substituted. During his recovery period, crew chief Mardy Lindley was suspended for one race for unsecured lug nuts; Dale Earnhardt Jr. served as substitute crew chief for the following race at Pocono, which Zilisch won.
Zilisch won the Xfinity Regular Season Championship with nine victories and secured an eighteenth consecutive top-five finish streak — a series record — before the streak ended at the fall Talladega playoff race. He advanced to the Championship 4 at Phoenix Raceway but was passed late in the final race by Jesse Love, who took the championship. Zilisch finished second in the series standings and won the Rookie of the Year award.
Zilisch made his Cup Series debut at Circuit of the Americas in 2025, driving the No. 87 for Trackhouse before being involved in a first-lap incident with teammate Daniel Suárez. He made additional Cup starts during the year, achieving a best finish of eleventh at Atlanta.
In December 2025, Trackhouse announced a multi-year Cup Series deal for Zilisch to drive the No. 88 full-time beginning in 2026. He also returned to endurance racing for the 2026 Daytona 24 Hours in the GTP class with Cadillac Whelen, where he and co-drivers Jack Aitken, Earl Bamber, and Frederik Vesti finished second overall by 1.5 seconds.
Zilisch's trajectory — karting world-level titles, IMSA endurance class victories, and a ten-win Xfinity campaign all before age nineteen — is without modern parallel in American motorsport. His formal path to the NASCAR Cup Series was the fastest by any driver through the Trackhouse developmental program.