"We are saddened to say we did not see that energetic, policy-driven Kirk when we met with him Oct. 3 for an endorsement interview," the newspaper editorial said. "While a stroke by no means disqualifies anyone from public office, we cannot tiptoe around the issue of Kirk's recovery and readiness."
Kirk suffered a stroke in 2012 and largely uses a wheelchair. Duckworth, an Army veteran who lost both legs in Iraq, also uses a wheelchair and prosthetic legs.
The Tribune endorsed Kirk in his successful Senate bid six years ago, and in his five previous 10th District House races.
Kirk's campaign challenged the newspaper's assessment of the senator.
"A low-blow and cheap shot by the Chicago Tribune that is not based on fact or reality," Kevin Artl, Kirk's campaign manager, said in a statement.
"The indisputable truth is that while Congresswoman Duckworth has been rated as one of the least effective members of Congress, Sen. Mark Kirk has been one of the most successful," Artl said, citing Kirk's work on the Export-Import Bank, securing money to fight violent crime and un-endorsing Trump in June.