In a statement, Vicky Cornell said: “I know that he loved our children, and he would not hurt them by intentionally taking his own life.
“Chris’ death is a loss that escapes words and has created an emptiness in my heart that will never be filled. As everyone who knew him commented, Chris was a devoted father and husband.
“What happened is inexplicable, and I am hopeful that further medical reports will provide additional details.”
Cornell, 52, was found dead in the bathroom of a Detroit hotel room on Wednesday night hours after the grunge band, which was in the middle of a US tour, had played a concert in the city.
A medical examiner initially ruled the singer’s cause of death to be suicide by hanging, but Mrs Cornell claimed his medication may have contributed.
She revealed her husband, a recovering addict, was taking the prescription drug Ativan, which treats anxiety and insomnia but whose side effects include increased depression and impaired judgement.
Mrs Cornell said she was concerned after speaking to him before and after the band’s gig: “I noticed he was slurring his words; he was different…he told me he may have taken an extra Ativan or two.”
Worried, she had asked security to check on her husband, who had tweeted a picture of the music venue shortly before the sold-out show, writing: “Finally back to Rock City!!!!.”
Cornell made no secret of his past drug and alcohol addiction, as well as periods of depression and agoraphobia, but he had reportedly been sober since 2002.
Family lawyer Kirk Pasich added they were unhappy at the medical examiner’s inference that Cornell “knowingly and intentionally took his life” before the results of toxicology tests were known.
“The family believes that if Chris took his life, he did not know what he was doing, and that drugs or other substances may have affected his actions,” Mr Pasich said.
Mrs Cornell married the singer in 2005 and the couple had two children together, daughter Toni and son Christopher Nicholas, while Chris had a child from another relationship.
Grammy Award-winning Cornell, who formed Soundgarden in 1984, was one of the leading voices of the 1990s grunge movement originating in Seattle.
The band had sold an estimated 22 million records worldwide by 2012.
He had also been the lead singer in the group Audioslave.
:: Anyone feeling emotionally distressed or suicidal can call Samaritans for help on 116 123 or email firstname.lastname@example.org in the UK.