Tiz the Law, a 3-5 morning line favorite, will start from the No. 17 post in the 146th Run for the Roses on Saturday, which was postponed from its traditional first Saturday in May due to the COVID-19 pandemic and will be held without fans.
Art Collector, who is unbeaten in four starts this year including two at Churchill Downs, suffered a minor injury to his left front and will be unable to compete in the 1-1/4 miles classic, owner Bruce Lunsford said on Tuesday.
"We didn't want to take any chances with a horse potentially this good," he said.
"The Derby means an awful lot to me so it's been kind of a tough day and night. But the horse is always the most important thing in all these things.
"We'll get another chance to have another day. We'll try and make it to the Preakness and maybe from there, the Breeders' Cup."
The absence of Art Collector is good news for Sackatoga Stable's Tiz the Law, who won last month's Travers Stakes in dominant fashion.
But the bay stallion with a white blaze will still face a formidable field.
Second choice Honor A.P. (5-1) will look to push Tiz the Law as will Authentic (8-1) and Thousand Words (15-1), which are both trained by Hall of Famer Bob Baffert.
Tiz the Law will also have to overcome its outside starting position as no horse has ever won the race from the 17th post, although a new starting gate at Churchill Downs and the absence of horses in gates No. 1 and 20 positions due to the 18-horse field could make that less of a challenge than in the past.
"I like it being on the outside," said Tiz the Law trainer Barclay Tagg.
"I didn't particularly want to be out that far but we have. He seems to handle everything that gets thrown at him.
"It gives you a chance if you have any speed at all. It gives you a chance." (Reporting by Rory Carroll in Los Angeles, editing by Pritha Sarkar)