Neighbors suspect the sign was defaced overnight on Monday, The Des Moines Register reported, in what was said to be an “extreme” incident.
The sign, which sat outside an address in Ankeny, Iowa, had Biden and Harris’s names covered with white paint and a swastika drawn on top in red, according to a police report.
Polk County sergeant Ryan Evans told the Register that no suspects were identified.
"That's obviously extreme," said Mr Evans. "It could be construed as a hate crime, which does elevate the severity."
No other incidents involving damaged campaign signs in Polk County have included swastikas or related violent symbols.
The incident comes as Mr Biden, the Democratic presidential nominee, suggested on Monday that Iowa and other states had moved within his reach.
Recent opinion polls have shown the former vice president statistically tied with president Donald Trump, who took Iowa in 2016, and campaigned in the state last week.
Mr Biden, for his part, said he was “going to be going to Iowa, be going to Wisconsin, I’m going to Georgia, I’m going to Florida and maybe other places as well,” as his campaign entered its final week.