Clear Lake is about 110 miles north of San Francisco by car — roughly two hours via US-101 north and then east on Highway 20 or Highway 29 through Napa. There is no public transit connection worth considering. Arriving by car is the only practical option.
Highway 29 from Napa is the most scenic approach and passes through Lake County's wine country. Highway 20 from Willits is faster from the north. The town of Clearlake on the eastern shore and Lakeport on the western shore are the main hubs.