John Kerry is expected to warn Sergei Lavrov that the referendum and Russia’s military intervention in Crimea could trigger concerted US and EU sanctions.
He has warned of “very serious steps” if Russia annexes the region.
Russia insisted at the UN on Thursday it did “not want war” with Ukraine.
During an emergency meeting of the Security Council, Moscow’s ambassador to the UN Vitaly Churkin defended the right of Crimea, which is predominantly ethnic Russian, to decide whether or not to join the Russian Federation.
Russia’s military intervention followed the fall of Ukraine’s pro-Moscow President Viktor Yanukovych on February 22.
John Kerry and Sergei Lavrov will meet at the US ambassador’s residence in central London.
It appears John Kerry will try to persuade Russia that it risks paying a heavy price in political and economic damage from American and European measures which could be triggered by Sunday’s referendum.
“If there is no sign of any capacity to be able to move forward and resolve this issue, there will be a very serious series of steps on Monday in Europe and here [in Washington] with respect to the options that are available to us,” he said before arriving in London on Friday.
While John Kerry seems to think the referendum itself may be all but unstoppable, he insists that it is what Russia does after that vote which counts – and Ukraine’s territorial integrity must not be permanently violated.
The talks are the last opportunity for face-to-face dialogue at such a senior level before the likely vote in Crimea, our correspondent says, which could determine whether what happens next edges Ukraine away from, or deeper into, a dangerous crisis.
John Kerry told lawmakers before his departure to London that the US was not eager to impose further sanctions on Russia.
“Our choice is not to be put in the position of having to do that. Our choice is to have a respect for the sovereignty and independence and territorial integrity of Ukraine,” he said.
The secretary of state said that he had spoken again by telephone with Sergei Lavrov on Thursday ahead of their Friday meeting, and that he and his Russian counterpart had been in almost daily contact over the past two weeks.
John Kerry has hinted at a possible compromise to the crisis by which the Ukrainian parliament would allow Crimea to hold a referendum on self-determination.
“The constitution of Ukraine requires that any effort by any entity within Ukraine to secede be done through the constitutional process,” John Kerry said.
He said that at the moment Russia did not “have the assets… necessary to be able to march in and take over Ukraine”, although he conceded that could change in future.
But correspondents say that the signs are not good for Friday’s talks, as both men have clashed in recent weeks and failed to agree on a number of US proposals.
Russia has refused to recognize the interim leadership that took over in Kiev with Viktor Yanukovych’s departure or participate in a contact group aimed at bringing the two countries together for talks.
In his appearance before the UN on Thursday, Vitaly Churkin said that it was Kiev that was “splitting its country into two parts”, not Moscow.
The referendum in Crimea, he said, had come about because of a “legal vacuum” in the country, and questioned why Crimeans should not be “afforded the opportunity” to decide on their future.
Ukraine’s interim PM Arseniy Yatsenyuk told the UN Security Council that his country was a victim of Russian aggression, producing a copy of the UN Charter to make his point that Moscow was violating it and several other international treaties.
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