Van Gisbergen, the three-time Australian Supercars champion making his Cup debut this weekend in the No. 91 Trackhouse Racing Chevrolet, set a blistering pace throughout the 50-minute session.
He remained at the top of the speed chart most of the practice and set his best average lap speed of 88.571 mph in the final minutes.
Cup veteran Denny Hamlin ended up second-fastest (88.262 mph) and former Formula 1 World champion Jenson Button was third (88.260 mph) driving the No. 15 Ford fielded by Rick Ware Racing and Stewart-Haas Racing.
Martin Truex Jr. was fourth and Christopher Bell fifth as Toyotas claimed three of the top-five spots.
Completing the top 10 were Kyle Larson, Corey LaJoie, Tyler Reddick, Ty Gibbs and Brad Keselowski.
Saturday’s practice was the first for the Cup series on a street course, a 2.2-mile, 12-turn course erected in the Grant Park area of downtown Chicago.
Almost 18 minutes into the practice, William Byron hit the wall in Turn 4 with the left-rear of his No. 24 Chevrolet and limped his way back to pit road.
About 30 minutes into the session, NASCAR displayed a caution when Austin Cindric spun and tagged the wall and dropped debris on the track. Ross Chastain went into the run-off area in Turn 4 but had no other problems.
Minutes after the practice restarted, Ricky Stenhouse Jr. slammed into the Turn 8 wall in his No. 47 Chevrolet but was able to make it back to pit road for repairs.
“I felt pretty good on the first half of the track, went to (Turns) 7 and 8 and back to (Turn) 12 is where I was losing a little bit of speed and I was just trying to push it a little bit in those areas,” Stenhouse said.
“I turned in a little too early in Turn 8, clipped the inside wall and then got the outside wall there. A little suspension damage – not sure how much yet.”
Minutes later, Justin Haley slid into the tyre barriers in Turn 4 but was able to continue on without the need for a caution.