"This month, I end my 3 years as U.S. Ambassador to #Qatar. It has been the greatest honor of my life and I'll miss this great country," she tweeted.
US ambassadorships typically last three years and a source close to Smith told CNN that she is leaving Qatar as planned now that her post is over.
Smith will also conclude her 25-year career in the foreign service once her post ends, the source said.
In May, Smith made headlines after taking the rare step of expressing frustration with the Trump administration for complicating American diplomats' work overseas.
Soon after FBI Director James Comey was fired, Smith tweeted: "Increasingly difficult to wake up overseas to news from home, knowing I will spend today explaining our democracy and institutions."
The exact target of her comment was unclear, but it was widely interpreted as criticism of President Donald Trump's dismissal of Comey.
Smith's departure comes days after Trump called on Qatar to stop funding terrorism, claiming credit for and endorsing the decision of Gulf nations to ostracize their neighbor, even as US Cabinet officials said their blockade is hurting the campaign against ISIS.
"We had a decision to make," Trump said, describing conversations with Saudi Arabia and other Gulf countries. "Do we take the easy road or do we finally take a hard but necessary action? We have to stop the funding of terrorism."
In doing so, the President's tone, if not his message, clashed with his most senior national security officials, highlighting the often mixed messages emerging from his administration since the Qatar crisis
began last week.
Deputy Chief of Mission at the US Embassy in Qatar Ryan Gliha is expected to serve as "Chargé D'Affaires ad interim" until a new ambassador is nominated, confirmed, and sworn in.