Riyadh's admission that the murder appeared to be a premeditated killing marked the latest twist in the official narrative from Saudi authorities.
The defense secretary made the remarks at a security conference in the island kingdom of Bahrain, across a bridge from Saudi Arabia, shortly before Saudi Foreign Minister Adel al-Jubeir decried what he said was a rush to conclusions before the investigation's completion.
Khashoggi, a Washington Post contributor and critic of Saudi policies, was killed after entering the Saudi consulate in Istanbul on October 2 to obtain paperwork for his marriage to his Turkish fiancee Hatice Cengiz.
Saudi Arabia has distanced its Crown Prince Mohammed bin Salman from the murder, and has fired five top officials and detained 18 Saudis during the ongoing investigation.
A man who called himself a friend of Khashoggi said they will never be at peace until those involved take responsibility and are brought to justice.
"The president has made very clear we will hold those responsible accountable, but that America has important, long-term, strategic interest in our relationship with the Kingdom of Saudi Arabia and that we are going to do both of those things at the same time - protect our interests and hold those responsible accountable", Pompeo said.
The Crown Prince on Wednesday called the Washington Post columnist's murder a "heinous crime that can not be justified". Mattis and others, meanwhile, have said the U.S.is providing key support to the Saudi-led coalition, and that the assistance is helping the kingdom improve its targeting.
He urged Riyadh to reveal who ordered the killing and the whereabouts of Khashoggi's body.
"Jamal Khashoggi's body still hasn't been found".
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Austrian Foreign Minister Karin Kneissl meanwhile suggested a joint European Union ban on arms exports to Saudi Arabia could help bring the brutal Yemeni conflict to an end. "The family wants to know and they want to perform their last duty", Mr Cavusoglu said, referring to hopes for the writer's burial.
The prince himself has faced worldwide criticism, with many officials charging he must have known about Khashoggi's killing, allegedly by Saudi security agents, and some saying he may have ordered his death.
Pro-government media in Turkey reported officials have such a recording, but its existence has not been confirmed.
Mattis suggested the killing threatened to undermine stability in the Middle East in his first substantive comments on a cascading geopolitical crisis that risks rupturing Saudi Arabia's relations with the West. The search was commissioned by the Turkish government's Water and Sewage Administration, the company said, and was regarding the Khashoggi case.
"There has been a hysteria in the media about Saudi Arabia's guilt", he said. "We will overcome" the consequences of the Khashoggi killing, he added.
The image, obtained by state television TRT and other media Wednesday local time, shows a black auto with a diplomatic license plate at an entrance to Belgrade Forest.
Turkish officials have told The Associated Press that investigators were looking into the possibility that the journalist's remains may have been hidden at those two locations.
Khashoggi, 59, a US resident and Washington Post columnist, was critical of the Saudi rulers. His death has been widely condemned by leaders around the world and many countries have warned of economic fallout as questions around his slaying swirl.