Kiev and Western governments have declared the referendum illegal, but have been powerless to stop it.
Voters have two options to choose from - but both imply Russian control of the peninsula.
On the surface, the second choice appears to offer the prospect of Crimea remaining with Ukraine.
However, the 1992 constitution which it cites foresees giving the region effective independence within Ukraine, but with the right to determine its own path and choose relations with whom it wants - including with Russia.
The streets of Simferopol have been largely calm in the days leading up to the vote, although the heavy presence of armed men, many wearing black balaclavas, has created an unnerving atmosphere in the normally sleepy town.
On Saturday night, about 30 men in balaclavas carrying automatic weapons barged into the Hotel Moscow, a Soviet-era hotel where many Western reporters covering Sunday's referendum are staying.
They said they had come to investigate an unspecified security alert and did not threaten anyone, but some witnesses saw it as a move to intimidate journalists.
Crimean Prime Minister Sergei Aksyonov, whose election two weeks ago in a closed session of the regional parliament is not recognised by Kiev, does not officially acknowledge that Russian troops are in control of Crimea - a position also maintained by Moscow.
(Read more: Ukraine accuses Russia of military incursion)
They say that thousands of unidentified armed men, visible across the region, belong to "self-defence" groups created to ensure stability.
Thousands of soldiers
But the Russian military, which leases the Crimean naval base of Sevastopol from Ukraine, has done little to hide the arrival of thousands of soldiers, along with trucks, armoured vehicles and artillery.
Masked gunmen surrounding Ukrainian military bases in Crimea have identified themselves as Russian troops.
Adding to tensions on the eve of the referendum, Ukraine's military confronted Russian forces which crossed Crimea's regional border on a remote sand spit, some 30 km (20 miles) off the mainland.
Crimea's separatist government said its own forces had moved to defend a gas pumping station. Ukrainian officials said no shots were exchanged.
What happens to Ukrainian forces in Crimea after Sunday's vote is one of many unanswered questions. Commanders are nervous about how Russia will go about taking control of military bases where Ukrainian forces are still armed.
Crimean authorities have said Ukrainian servicemen will have the choice of surrendering their weapons and walking away peacefully or joining pro-Russian local forces.
In the run-up to the referendum, the worst violence in Ukraine has been in the east, where acting president Oleksander Turchinov said there had been three deaths in two days.
He also said there was "a real danger" of invasion by Russian troops across the eastern border. The area has a large number of Russian-speakers - significant since Putin has vowed to protect ethnic Russians and Russian-speakers in Ukraine.