Khashoggi, who has been living in self-exile in the United States, entered the consulate's premises at around 1pm in what seemed to be a routine visit to sort out paperwork, before disappearing, the Arabic-language Arab21 news website reported on Tuesday, quoting his fiance.
The prominent columnist for the Washington Post has long criticised the Saudi government's reform programme under the auspices of Crown Prince Mohammed bin Salman.
"He entered at 1pm [11am BST] and hasn't surfaced since then. I have no media statements to make at this point, but I have contacted Turkish authorities for help," Khashoggi's fiancee, who did not want to be identified by name, said.
According to the fiancee, Khashoggi visited the Saudi consulate in Istanbul last week, but was asked to return on Tuesday to complete an application related to family matters, according to a journalist at Arabi21 news website, who has spoken to her.
The fiancee, who is a Turkish citizen, said he entered the consulate's Saudi nationals section, while she waited for him at the foreigners' hall for several hours until the consulate closed. The consulate's hours of operation are 9am to 3pm.
Turkish and Saudi authorities, including the Istanbul consulate and the Saudi Embassy in Washington, did not immediately respond to requests for comment, according to a Reuters report.
Khashoggi, 59, is a former editor-in-chief of Saudi newspapers al-Arab and Watan. He previously served as the media advisor to Prince Turki al-Faisal during his tenure as ambassador in London and Washington.
The seasoned journalist studied at Indiana State University and has been based in Washington DC since he fled Saudi Arabia in 2017 over fears of the new government's crackdown on critical voices.
Khashoggi is considered a Saudi nationalist, and before leaving Saudi Arabia in September 2017, he was seen as close to the royal court.
However, friction between him and the kingdom's rulers began to emerge after comments at the Washington Institute for Near Eastern Policy, warning that Saudi Arabia should be "rightfully nervous about a Trump presidency".
Authorities informed him that he was banned from writing and tweeting soon after. Worried by the actions, Khashoggi decided to leave the country.
Since then, he has primarily been living in the US capital, writing for the Washington Post. His columns include criticising Saudi Arabia's policies towards Qatar and Canada, the war in Yemen, and a crackdown on the media and activists.
"I have left my home, my family and my job, and I am raising my voice," he wrote in September 2017. "To do otherwise would betray those who languish in prison. I can speak when so many cannot."
Eli Lopez, senior editor of Global Opinions at the Washington Post, said the newspaper is "very concerned" about where Khashoggi may be after failing to reach him on Tuesday.
"We are monitoring the situation closely, trying to gather more information," Lopez said in a statement.
He added, "It would be unfair and outrageous if he has been detained for his work as a journalist and commentator. Jamal is a great writer and insightful political observer, deeply committed to the open exchange of ideas; we are honored to have his point of view be part of our Global Opinions. We hope that he is safe and that we can hear from him soon."
Saudi Arabia has recently stepped up politically-motivated arrests, prosecution and conviction of peaceful dissident writers and human rights campaigners.
The US State Department said it was aware of the reports on Khashoggi's apparent disappearance.
"We have seen these reports and are seeking more information at this time," a US official told MEE via email.
According to a friend of Khashoggi, the journalist's Saudi wife divorced him following his fallout with the Saudi authorities.
He was visiting the Istanbul consulate to obtain proof of his divorce required by Turkish authorities to marry his fiancee.
A campaign to raise awareness of Khashoggi's disappearance quickly emerged online, with social media users tweeting the hashtag "JamalKhashoggikidnapped" in Arabic.
Al Jazeera Arabic has reported that Turkish police have opened an investigation into the matter.
Powerful Crown Prince Mohammed bin Salman led a purge against businessmen and fellow royals last year, detaining dozens of powerful figures for alleged corruption until they agreed to financial settlements.
Last year, Saudi authorities also reportedly held Lebanese Prime Minister Saad Hariri and put him under house arrest. Both Hariri and Riyadh denied the reports, but European officials, including French President Emmanuel Macron, have confirmed that the prime minister was detained by the Saudis.
Saudi officials have also intensified security measures in the oil-rich Eastern Province.
Eastern Province has been the scene of pro-democracy protests since February 2011.
Protesters demanding reforms, freedom of expression, release of political prisoners, and an end to economic and religious discrimination against the oil-rich region have been met with military crackdown.
Over the past years, Riyadh has also redefined its anti-terrorism laws to target activism.
In January 2016, Saudi authorities executed Shia cleric Sheikh Nimr Baqir al-Nimr, an outspoken critic of the policies of the Riyadh regime. Nimr had been arrested in Qatif in 2012.
While bin Salman has led a modernisation campaign to counter the kingdom's image as an ultraconservative society with a repressive government, rights groups say the crackdown against human rights activists has escalated.
"The Saudi government appears determined to leave its citizens without any space to show even rhetorical support for activists jailed in this unforgiving crackdown on dissent," Sarah Leah Whitson, Middle East director at Human Rights Watch, said in a statement earlier this year.