Kerry also warned against the Russian parliament ratifying the vote, which he said would amount to a "backdoor ratification" - a move that would trigger sanctions and escalate the biggest East-West showdown since the 1989 fall of the Berlin Wall.
Despite six hours of talks, including two long tete-a-tete walks in the grounds of the lavish US ambassador's residence in central London, Lavrov said Russia and the West remained far apart on Ukraine.
And he hinted that Moscow was now resolved to bring Crimea under its eventual control.
"Everyone understands - and I say this with all responsibility - what Crimea means to Russia, and that it means immeasurably more than the Comoros [archipelago] for France or the Falklands for Britain."
Kerry again warned that the international community would not recognise the results of the referendum and said if it went ahead, "there will be some sanctions, there will be some response".
British Foreign Secretary William Hague said the failure of the talks in London was "deeply disappointing" and he called for "tougher restrictive measures."
Asked when the US would respond to the referendum, White House spokesman Jay Carney said: "I think, without putting too fine a point on it, I'd say quickly."
Kerry insisted again that Washington did not want to impose sanctions on Moscow, but said even just the threat was causing Moscow stocks to tumble.
They plunged to a four-year low on Friday as jittery investors dumped their holdings ahead of the referendum, while the ruble again fell against major currencies.
US stocks also took a hit, and oil prices rose.
Ukraine, a former Soviet republic of about 46 million people, remained a tinderbox as more than 8000 Russian troops staged drills near its eastern border while Nato and US reconnaissance aircraft and fighters patrolled the skies of its EU neighbours to the west.
Russia still refuses to recognise the legitimacy of the Western-leaning team that has taken power in Kiev, a move that threatens to shatter Putin's dream of rebuilding an empire dominated by Moscow.
Today's vote gives residents of Crimea - a rugged region that has housed tsarist and Kremlin navies since the 18th century - only two choices: joining Russia or "the significant strengthening of their autonomy within Ukraine".
The peninsula's self-declared leaders have already predicted an easy victory and the region is largely expected to vote in favour of joining Russia despite discontent from the Muslim Tatar minority that makes up 12 per cent of Crimea's total population of two million.
- AAP
