Mrs Clinton will meet Turkish leaders as well as Syrian opposition activists.
They are expected to discuss preparations for a transition of power in Syria if the government of President Bashar al-Assad falls.
The UN says there has been a surge in the number of civilians fleeing violence in Syria, especially from the northern city of Aleppo.
Turkey, like all of Syria’s neighbours, is dealing with a growing humanitarian crisis as thousands of refugees flood across the border.
Rebels in Aleppo say they are preparing a counter-attack after withdrawing from the strategic south-west district of Salah al-Din under heavy bombardment.
The BBC’s Bethany Bell in Istanbul says high on the agenda of Mrs Clinton’s talks there is how to best co-ordinate support for the fractured Syrian opposition.
US officials say the secretary of state wants to understand Turkey’s position and its concerns as conditions in Syria deteriorate.
She is also expected to announce more humanitarian aid for those fleeing the violence.
Turkey is currently supporting more than 50,000 Syrian refugees with more arriving every day.
The talks will also focus on plans for what US officials call “the day after Assad”, our correspondent says, taking steps towards a future Syria that Washington hopes will be pluralistic and democratic.
Among US concerns are reports that a growing number of al-Qaeda linked militants are fighting alongside rebels in Syria.
US intelligence officials quoted by AP news agency said at least 200 militants linked to al-Qaeda are already operating in Syria, and their numbers are growing as foreign fighters enter the country.
US officials fear they could establish a presence similar to that in Iraq, which could be hard to defeat if rebels eventually oust President Assad.
Analysts say it could be one reason why Washington has been reluctant to offer military assistance to the anti-Assad insurgency.
Sporadic violence was reported around Syria on Friday.
Journalists from Reuters news agency reported seeing residents fleeing Aleppo with cars packed with possessions, taking advantage of a lull in the fighting.
AFP news agency reported that a bakery in the city’s eastern Tariq al-Bab district had been hit by a shell, killing about 12 people and injuring at least 20.
State news agency Sana also reported that government forces had repelled a rebel attack on Aleppo’s international airport.
The opposition Syrian National Council said part of Aleppo’s 13th-century citadel had been damaged by shelling.
Activists also reported fighting in suburbs of the capital, Damascus.
President Assad is facing down stiff international pressure to step aside despite months of anti-government protests and worsening violence.
He has suffered a string of high-status defections, including his former Prime Minister Riad Hijab, who fled to Jordan earlier this week.
Source: BBC News