For the past three years the pole-sitter has surrendered the lead on the opening lap. That included Palou, second on the grid, overtaking Chip Ganassi Teammate Scott Dixon before one circuit was completed on the 2.5-mile (4km) oval last year.
"I'm going to control the first lap with the first two corners, because it's almost guaranteed that I'm not going to lead the first lap," Palou said. "So I'm ready for not to lead the first lap. And hopefully we can lead the second one."
Palou led 42 of the first 68 laps last year, but when a caution forced him to stop for fuel when the pits were closed, he was left at the back of the field and he was unable to recover, eventually finishing ninth in the race won by Sweden's Marcus Ericsson.
It's just one example of the surprises that can upend the best-laid plans over the course of 500 intense miles.
"There's so many things out of your control in this race," Palou said. "If it was another race, and I was on pole, I'd be like, 'Oh yeah, we're going to control and do this and that.'
"Not this one. You can control your first run for sure, which is really important to have a slower race that way that you don't have to rush to get into the top 10 and save fuel at the end or do crazy stuff to overtake.
"But as soon as the first pit stop is going, we are losing control of everything."
Palou leads the fastest field in Indianapolis 500 history. His four-lap average of 234.217 mph (376.94 Km/h) crushed the previous pole mark, and the three cars on the front row all averaged above 234 mph for the first time.
Just 2.121 seconds separate Palou from the 33rd and final qualifier Jack Harvey.
Ed Carpenter Racing's Rinus VeeKay of the Netherlands is second on the grid and Sweden's Felix Rosenqvist of Arrow McLaren, who topped both of the first two qualifying sessions, was third-quickest in pole qualifying.
While Palou is well-aware that the pole sitter has won the race just once in the past 13 years, he's still hoping he can buck that trend and add the Indy 500 to the GMR Grand Prix title he won the road course at the Indianapolis Motor Speedway earlier in May.
Meanwhile Mexico's Pato O'Ward starts from fifth on the grid and will be hoping to go one better than his runner-up finish to Ericsson last year.
He's joined on the second row of the grid by AJ Foyt Racing's Santino Ferrucci and Dixon - a six-time IndyCar champion who started from pole the past two years.
New Zealand's Dixon, who won the Indy 500 in 2008, endured frustration the past three years as he tried to win again. He led 111 of 200 laps in 2020, was knocked off stride by an early race caution in 2021 and received the pit lane penalty last year.
Kanaan and Castroneves return
Dixon isn't the only veteran in the hunt. Tony Kanaan, the 2013 winner, and four-time Indy 500 champion Helio Castroneves - both of Brazil - are both 48 years old.
Three drivers - David Malukas, Sting Ray Robb and Christian Lundgaard - are 21 and could break the record for youngest winner set by 22-year-old Troy Ruttman back in 1952.
The strong Chip Ganassi challenge led by Palou also features two-time winner Takuma Sato of Japan, who is driving only ovals for the team this year and qualified eighth-fastest, two spots ahead of defending champion and Ganassi teammate Ericsson.
Palou is the only Ganassi driver who hasn't won the Indianapolis 500, and Sato and Dixon topped the times in Friday's final practice session.
Arrow McLaren, with Rosenqvist and O'Ward leading the way, have been impressive in the build-up to the race and boast two previous winners among this year's top-10 qualifiers in Alexander Rossi and Kanaan.
