Voting at more than 9,000 polling stations across the country began at 0100 GMT (0630 IST) and will continue until 1500 GMT (2030 IST), according to the country's central election commission.
Karimov, who has ruled the country since before the collapse of the Soviet Union, faces three other opponents put forward by parties in the Uzbek parliament that are openly supportive of his presidency.
Akmal Saidov, put forward by the Democratic National Renaissance Party, faced Karimov in the country's last presidential poll in 2007, but claimed less than three per cent of the vote as Karimov took close to 90 per cent.
Almost 21 million people are eligible to vote in the most populous of the five former communist Central Asian countries that gained independence in 1991, according to the central election commission.
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Exit polls are banned under Uzbekistan's restrictive laws while a turnout of 33 per cent is required for election results to be considered legitimate by the commission.
More than 300 international observers from 43 different countries are participating in the vote. The Organisation for Security and Cooperation in Europe is expected to provide its assessment of the ballot tomorrow.