No. US-2 crosses onto South Hero on a causeway from Milton and carries on north through the chain by bridge, so the whole county is reachable by car. There is also a year-round ferry between Grand Isle and Plattsburgh, New York, which crosses in about twelve minutes.
Honestly, the lake is the point. Beyond it there are apple orchards and small farms, the Hyde Log Cabin on Grand Isle from the 1780s, quiet cycling on flat back roads, and birdwatching around the Missisquoi wetlands north of the islands. It is a place for slow days rather than a list of attractions.
Late spring and early autumn are lovely and much emptier, with good light over the water and the Adirondacks across it. Winter is stark: many seasonal businesses close, though ice fishing shanties appear on the bays in a cold year.
Close enough to be a day trip in either direction. South Hero is roughly 30 to 40 minutes from Burlington by US-2 and I-89, so people staying on the islands regularly drive in for dinner, the airport or a museum.
Live prices for every hotel and inn in the area — free cancellation, updated daily.