VERMONT ROUTE 100
Stamford, Vt., to Newport, Vt., 216 miles
Snaking through the center of Vermont all the way from the Massachusetts border to the Canadian one, Route 100 feels less like a state highway than one long, rambling backcountry path. A strict billboard ban preserves every vista as the road winds between the peaks of Green Mountain National Forest and passes through quaint valley towns like Hyde Park and Weston (population 631). With only farm stands, country stores, and covered bridges breaking up the landscape, you'll consistently feel 200 miles from the 21st century.
Don't miss: The seven-mile stretch through Granville Gulf State Reservation, a favorite for leaf peepers, is also home to the multitiered, 35-foot-tall Moss Glen Falls, which can be seen from the road.
Trip tip: The Vermont Curiosities guidebook ($16) goes beyond foliage, introducing travelers to little-known gems around the state, from roadside barbecue joints to hole-in-the-wall museums.
Where to stay: The Old Red Mill Inn, in the heart of Wilmington, retains rustic charm from its previous life as a sawmill (18 N. Main St., Wilmington, oldredmill.com, from $70). Homemade cookies and intricate quilts create a homey vibe at the Brass Lantern Inn, but be sure to leave the property from time to time to explore Stowe's award-winning restaurants (717 Maple St., Stowe, brasslanterninn.com, from $99).
GREAT LAKES SEAWAY TRAIL
Massena, N.Y., to West Springfield, Pa., 518 miles
Consider this scenic waterfront byway an inland version of California's Route 1—minus the traffic. Among the highlights of the 500-plus-mile drive: the St. Lawrence Seaway's imposing Eisenhower Lock, the 28 historic lighthouses skirting the shores of the Niagara and St. Lawrence Rivers and Lakes Ontario and Erie, and the country's ultimate aquatic spectacle, Niagara Falls. Forty state parks along the way supply ample spots for camping, as well as opportunities for everything from bird-watching to shipwreck diving.
Don't miss: Presque Isle State Park, a sandy, 3,200-acre peninsula near Erie, Pa., has miles of untouched beaches to explore.
Trip tip: Ditch the tired car games in favor of the Seaway Trail's new geocaching trail: a high-tech treasure hunt where you use a GPS unit to locate natural and historic landmarks. Supplies are available at the Great Lakes Seaway Trail Store.
Where to stay: The Georgian-style Hillcrest Inn (1 Hillcrest St., Niagara Falls, N.Y., hillcrestniagara.com, from $119) sits on a quiet block just out of earshot of the boom of Niagara Falls; guests can eat breakfast on a private balcony with views of the upper rapids. The Boothby Inn is a restored 1888 Victorian home in the heart of downtown Erie, mere minutes from the bay (311 W. 6th St., Erie, Pa., theboothbyinn.com, from $130). In the aptly named Shakespeare room, the decorative tiles lining the fireplace depict scenes from some of the Bard's famous plays.
BLUE RIDGE PARKWAY
Waynesboro, Va., to Cherokee, N.C., 469 miles
One of the New Deal's most ambitious endeavors, this curvaceous "park-to-park highway" links Virginia's Shenandoah National Park with North Carolina's Great Smoky Mountains National Park via dozens of hairpin turns and 26 tunnels cut through Appalachian granite. Spot a 19th-century farm or postage-stamp-size town at the bottom of a verdant mountainside and you'll realize how seemingly unchanged the road remains since its inception in 1935.
Don't Miss: Concerts of traditional Appalachian banjo and fiddle music start at 10 a.m. Sunday through Thursday at the Blue Ridge Music Center, located in Galax, Va.
Trip Tip: Banjo music is the ideal soundtrack for this drive. Get in the mood with Drive Time: Blue Ridge Parkway ($8), a CD compilation of Appalachian music with songs by Aaron Copland and John Williams.
Where to stay: Step back in time with a visit to the Mast Farm Inn, where you can admire the meticulously kept grounds and gardens from a porch rocking chair or sharpen your culinary skills at the Mast Farm Inn School of Cooking (2543 Broadstone Rd., Banner Elk, N.C., mastfarminn.com, from $99). The Bearskin Lodge on the River is situated along a trout stream on the edge of Great Smoky Mountains National Park (840 River Rd., Gatlinburg, Tenn., thebearskinlodge.com, from $45). Log and stone accents give the property an appropriately rustic look.
HISTORIC ROUTE 66
Chicago to Los Angeles, 2,448 miles
Immortalized by John Steinbeck in The Grapes of Wrath, this original mega highway has long personified the American dream of escaping hard times and making it big out West. Although you won't find the 84-year-old road on maps anymore (it's been replaced by segments of the Interstate Highway System), you can still follow the classic drive from the small towns of the Midwest and Great Plains through the deserts of the Southwest and on to Los Angeles.
Don't miss: The 400-mile-long Oklahoma portion best embodies the retro spirit most 66 travelers are looking for, with ghost towns like Texola and sightings of Americana such as the 66-foot-tall soda bottle marking Pops restaurant in Arcadia.
Trip tip: Find (and stay on) the historic route with Here It Is! The Route 66 The Map Series ($12), eight foldout maps with full driving directions and recommendations for the most worthwhile stops.
Where to stay: Wicker Park Inn's brick rowhouse has been a fixture of Chicago's leafy Wicker Park neighborhood since the 1890s (1329 N. Wicker Park Ave., Chicago, wickerparkinn.com, from $139). The eight themed guest rooms—from Cape Cod to Provence to Tuscan—are appealingly understated, not kitschy. On the Oklahoma leg of Route 66, the two buildings that compose the present-day Pollard Inn (124 W. Harrison Ave., Guthrie, Okla., pollardinn.biz, from $150) were christened as the Guthrie Savings Bank and the W.N. Wallace Pharmacy in the early 20th century. The bank's original vault stands among multitudes of other historic relics that decorate the halls and guest rooms.
DOOR COUNTY, WISCONSIN
Milwaukee to Peninsula State Park, 170 miles
The upper Midwest does not leap to mind as a hotbed of culinary genius, but you might want to think again. Across western Wisconsin, there's a minor revolution afoot, a movement to bring back the traditional pies, small-batch gins, Cornish pasties, and Danish kringles the area was once known for. On any given Saturday, particularly on the Door Peninsula sandwiched between Green Bay and Lake Michigan, you're almost guaranteed to happen upon roadside fish boils and farm stands loaded with fresh apples, juniper berries, Montmorency cherries, and, of course, artisanal cheeses (it is Wisconsin, after all).
Don't miss: Fruit wines—including raspberry, cherry, and peach—are gaining popularity among oenophiles, and the county's top-rated quaffs are at Door Peninsula Winery (5806 Hwy. 42, dcwine.com). Just north of the town of Sturgeon Bay, the 36-year-old winery recruited California vintner Paul Santoriello, who has made wines for the likes of David Bruce Winery, a pioneer of cutting-edge production techniques.
Trip tip: Indulge in local specialties, like maplewood-smoked whitefish from Charlie's Smokehouse, where the Voight family has been smoking fish since 1932 (12731 Hwy. 42, charliessmokehouse.com, whitefish $5.50 a pound).
Where to stay: The Feathered Star Bed & Breakfast boasts an address in Egg Harbor, one of our newly crowned "Coolest Small Towns in America" (6202 Hwy. 42, Egg Harbor, featheredstar.com, from $120). Named after the historic "feathering" quilting design, the inn has six guest rooms that play into the theme by highlighting unique quilting motifs. At the Lodgings at Pioneer Lane, seven elegant and spacious rooms are each appointed to send guests on a vacation within their vacation: The Sea Chest Room channels Nantucket, the Cabin Room alludes to the Adirondacks, and the Leaf Room is reminiscent of Scandinavia (9998 Pioneer Ln., Ephraim, lodgingsatpioneerlane.com, from $80).