In a blistering speech, Pence on Thursday accused China of military aggression, commercial theft and rising human rights violations as he cast the Asian power as a villain bent on interfering in upcoming US polls.
"The relevant speech made unwarranted accusations against China's domestic and foreign policies and slandered China by claiming that China meddles in US internal affairs and election," Chinese foreign ministry spokeswoman Hua Chunying said in a statement.
"This is nothing but speaking on hearsay evidence, confusing right and wrong and creating something out of thin air. The Chinese side is firmly opposed to it," she said.
Expanding on complaints aired by President Donald Trump at the United Nations last week, Pence accused China of waging an "unprecedented effort to influence American public opinion" ahead of critical congressional elections on November 6, and wanting "a different American president."
Relations between the world's two largest economies have plummeted in recent weeks with Trump placing $250 billion in tariffs on Chinese goods, in part over charges that Beijing forces US companies to hand over technological know-how.
"It is very ridiculous for the US side to stigmatise its normal exchanges and cooperation with China as China interfering in its internal affairs and elections," Hua said.
"China always follows the principle of non-interference in others' internal affairs and we have no interest in meddling in US internal affairs and elections," she said.
"We urge the US to correct its wrongdoing, stop groundlessly accusing and slandering China and harming China's interests and China-US ties."