The town has officially been deemed an island, according to the Sonoma County Sheriff's Office.
The evacuation orders affect about two dozen communities stretching dozens of miles along the river, including Guerneville, with a population of more than 4,500. By Wednesday night, the river could crest at 46 feet, making it the sixth highest on record.
Several other Northern California creeks and rivers are expected to crest before the storm eases out of the region.
There are fears of avalanches in the Sierra Nevada mountains after seven feet of snow fell over the past three days. A flood warning is in effect for parts of the area, the weather service said. More than 8 feet of water inundated the 23-room business.
More rain is forecast through Sunday - except on Thursday. On Wednesday, television news footage showed muddy brown water almost swallowing his ground-level unit and much of the tiny town of Guerneville, part of Sonoma County's famed wine country and a popular tourist destination.
While no flood-related serious injuries or deaths were reported in Sonoma County, a man about 150 miles (330 kilometres) to the north in Ferndale died trying to reach three children.
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"Other rivers in the area are also going to see major flooding; the Navarro River is now above flood stage and is forecast to crest at 35.4 feet at Navarro late [Tuesday]". The record is 49.5 feet, set in 1986, the National Weather Service says.
"The river is on its way down" and expected to drop below flood stage by 3 a.m. local time on Friday, Sonoma Valley Fire and Rescue Battalion Chief Spencer Andreis told an afternoon news conference. "You will not be able to get into or out of town without a boat today".
The Russian River in the wine country north of San Francisco reached its highest level in 25 years Wednesday night and Sonoma County officials say it won't return to its banks until late Thursday.
"(The proclamation) is not just a sign that we have insufficient resources or we're overwhelmed, but instead that we recognize the true potential worst-case scenario here and we want to make sure that we're mobilized effectively and fully to deal with that threat", Godley said.
Residents used anything they could find to get out and about and to reach people who were stranded. "Do not try to go through any water over a foot high because you never know what you're going to find". "Too many people are driving into water", Baxman told the Press Democrat newspaper.
"I could not afford to buy flood insurance", she said.
Orr moved to Guerneville about five years ago, driven out of San Francisco by rising costs.