The sheer volume of insects reduced visibility, and turned the road surface of the bridge over the Susquehanna River, in Lancaster County, into a treacherous, slippery mess.
Piles of mayflies up to 2ft (0.6m) deep were seen the morning after.
Immature mayflies live in water, before hatching as adults to mate in swarms.
The bridge was closed late on Saturday, reopening early on Sunday, police said.
"It was like a blizzard in June, but instead of snow, it was mayflies," Wrightsville Fire Chief Chad Livelsberger told LancasterOnline.
"They were getting in our mouth. We had to close our eyes. We had to swat them away. Even when we got back, it felt like bugs were crawling in you."
Spectacular swarms of mayflies are not uncommon - last year one in Wisconsin became so big it appeared on local radar as rain.
A dense swarm of mayflies caused motorcycle crashes and the overnight closure of a bridge in the US state of Pennsylvania.