The 60-year-old judge and producer is recuperating from spinal surgery after he suffered an accident involving his new electric bike last weekend.
Clarkson, 38, revealed on Instagram: “My friend, Simon Cowell, is doing better now but was in an accident and won’t be able to make Tuesday and Wednesday’s live shows for AGT.
“But no worries America, someone far wiser, cooler, and hotter is taking his seat! The unbelievably amazing Kelly Clarkson. You’re welcome in advance.”
Since U Been Gone singer Clarkson rose to fame after winning the first series of TV talent show American Idol in 2002, with Cowell among the judges.
She has been a judge on rival singing talent show The Voice since 2017 but will be making her debut on the America’s Got Talent judging panel as she fills in for TV’s Mr Nasty.
Clarkson will join judges Howie Mandel, Heidi Klum, Sofia Vergara for the live quarter final shows in the 15th series of AGT.
The show’s broadcast has been impacted by the coronavirus pandemic and subsequent lockdown but is returning to TV this week.
Cowell underwent surgery in the early hours of Monday after breaking his back.
The Britain’s Got Talent creator was trying out a new electric bike at his Malibu home with his family when the incident occurred.
He tweeted after undergoing six hours of emergency surgery to pin his spine: “Some good advice... If you buy an electric trail bike, read the manual before you ride it for the first time. I have broken part of my back. Thank you to everyone for your kind messages.
“And a massive thank you to all the nurses and doctors. Some of the nicest people I have ever met. Stay safe everyone. Simon.”
Cowell was treated in hospital in 2017 after he fainted and fell down the stairs at his London home. Security guards who found him feared he had broken his neck and he was tested for brain injuries.
The heavy smoker – father to six-year-old son Eric with girlfriend Lauren Silverman – called the health scare a wake-up call and went on to overhaul his unhealthy lifestyle.
Cowell said afterwards he was taking steps to change his work-life balance, cutting down on late night work calls, and has gone on to lose a significant amount of weight by cutting out red meat, sugar, dairy and gluten from his diet.