Ukraine and Lithuania have also threatened to pull out of the world police organisation if the Russian general is elected president.
A growing chorus of critics is calling on Interpol to reject a Russian candidate to lead the organisation, over fears Moscow could abuse the role to target political opponents.
The Kremlin has denounced what it says was "interference" in the vote, set for Wednesday at the close of Interpol's annual conference in Dubai, to replace its former president now detained in China on bribery charges.
Moscow's critics have raised concerns over Russia's previous applications for Interpol "Red Notices", or international arrest warrants, to target those who have fallen foul of the Kremlin.
Alexander Prokopchuk, a Russian interior ministry official and current Interpol vice president, appears to be the favourite for the position.
In an open letter this week, a bipartisan group of US senators said choosing Prokopchuk would be like "putting a fox in charge of a henhouse".
"Russia routinely abuses Interpol for the purpose of settling scores and harassing political opponents, dissidents and journalists," they wrote.
The senators said Prokopchuk has been "personally involved" in this strategy.
Delegates from Interpol member countries will elect a new president to replace Meng Hongwei, who went missing in his native China in September. Beijing later said Meng resigned after being charged with accepting bribes.
The other candidate running is South Korea's Kim Jong-Yang, the acting president, and whoever is elected will serve out Meng's term until 2020.
British foreign office minister Harriet Baldwin on Tuesday told parliament that London would support the South Korean's bid.
"We always seek to endorse candidates who have a history of observing standards of international behaviour," she said.
A US State Department spokesperson said Washington wanted Interpol to work in a "neutral, objective" way, without referring to any candidate.
"We are actively and broadly engaged with Interpol member states to underscore the need to elect someone who will promote, not undermine, the values and practices that make Interpol such a vital international body."
Anti-Kremlin figures have raised concerns, including Alexei Navalny, the Russian opposition leader who has been repeatedly jailed by authorities.
"Our team has suffered from abuse of Interpol for political persecution by Russia," Navalny wrote on Twitter. "I don't think that a president from Russia will help to reduce such violations."
The controversy also comes amid security concerns over accusations of Russian agents carrying out a spy poisoning in Britain and attempting to hack the network of the global chemical weapons watchdog.
Ukraine, deeply at odds with Moscow over its annexation of Crimea and support for separatists, threatened to pull out of Interpol if Prokopchuk prevailed. Lithuania also said it would consider withdrawing from the network.
Russian presidential spokesman Dmitry Peskov dismissed the US senators' letter as a "vivid example" of an attempt to interfere in the vote.
Moscow's interior ministry denounced a "foreign media campaign aimed at discrediting Russia's candidate".
But two foes of Russian President Vladimir Putin, who have been targeted by international arrest warrants sought by Moscow, also said Tuesday they were launching a bid to get Russia suspended from Interpol for abusing the agency.
The legal challenge was announced by financier Bill Browder, named in multiple Interpol warrants, and Mikhail Khodorkovsky - a former oil baron who spent 10 years in a Russian jail and now lives in London exile.
"The Interpol constitution has very specific rules which forbid countries who are serial abusers from using the system," Browder told reporters.
Browder, briefly arrested in Spain this year under a Moscow-issued Red Notice, said the Russian candidacy was an attempt by Putin to "expand his criminal tentacles to every corner of the globe".
Browder fought for - and in 2012 secured - US sanctions against Russian officials believed to be involved in the death of his tax consultant, Sergei Magnitsky.
Magnitsky died in jail in 2009 after accusing Russian officials of a $230 million tax fraud.