Who knew the Pennsylvania Turnpike led to so many masterpieces? Just off the toll road, you will find an architectural wonder, Pop Art haven, papal treasures and more. The starting point on this road trip? The city of Pittsburgh and a tour of its museums.

Pittsburgh's Andy Warhol Museum (www.warhol.org) is celebrating its 15th anniversary this year, kicking it off with a 24-hour opening party for a Marilyn Monroe exhibit that runs through early January. It includes photography, Pop Art and film from Warhol and others, including Richard Avedon and Henri Cartier-Bresson. Warhol (born Andrew Warhola in 1928) grew up in Pittsburgh and graduated from what is now Carnegie Mellon University. Work from "The College Years" is also on display through early next year. The permanent collection of this six-floor gallery includes thousands of Warhol's paintings, drawings, films, sculptures, prints and more, plus the artist's archives. Definitely spend some time in the playful "Silver Clouds" balloon room installation.

In the city's market-filled Strip District is the Heinz History Center (www.heinzhistorycenter.org), which boasts a major exhibition of Vatican art that will only hit three cities in the US this year. The 10,000-sq-ft exhibit, the largest Vatican show to come to North America, runs through 9 January and features works by Michelangelo and Bernini, tools used to work on the Sistine Chapel, and even a reliquary with the remains of Saint Peter and Saint Paul. The display of sculptures, mosaics, paintings and artifacts includes 200 pieces. Get your timed-entry tickets in advance.

Switch gears to contemporary art, housed at the unique Mattress Factory (www.mattress.org), which supports artists-in-residence and room-sized works. James Turrell's light installations toy with your sense of space and dimension, and Yayoi Kusama makes your reflection part of the art when you step inside her mirror-clad, polka dot mannequin room. Through late February, the Mattress Factory is home to an exhibit of painting, photographs, sculpture and other works by Cuban artists exploring issues of race, racism and discrimination.

Head out of the city for a 90-minute drive through rolling, wooded hills to Fallingwater (http://fallingwater.org), the residential masterpiece that resurrected the career of American architect Frank Lloyd Wright in the late 1930s. Pittsburgh was very much a smoky steel mill- city when Wright designed this weekend retreat for the Kaufmann family. Today, the house is a museum and sits virtually hidden in the windy Laurel Highlands of western Pennsylvania. Known for his philosophy of an organic architecture that does not disrupt nature, Wright built Fallingwater on top of a waterfall, with sections of the home jutting out from the hillside and hovering over the creek below. Wright left boulders in place - your mandatory tour guide will point out one that forms part of a fireplace inside the home - and used local sandstone in the construction.

Drive another 6 miles through the countryside to another Wright house-turned-museum, Kentuck Knob (www.kentuckknob.com). Part of his Usonian series, one-floor structures for families of modest means, Kentuck Knob was designed in 1954, when Wright was in his late 80s. The hexagonal home built of honey-colored swamp wood and sandstone includes features he invented - radiant floor heating and the carport - plus Wright-made furniture. After touring the home, take a stroll through the sculpture garden, with works by Andy Goldsworthy and Claes Oldenburg, and two slabs of the Berlin Wall. Reserve tour times for both Wright homes a few weeks in advance.

If you still feel like driving, another half hour and you will hit Uniontown, where the State Theatre Center for the Arts (www.statetheatre.info), a 1922 movie and vaudeville theatre designed by architect Thomas W Lamb, puts on concerts, musicals and classic films. Or stop by Greensburg on your way back to Pittsburgh for its Westmoreland Museum of American Art (www.wmuseumaa.org), featuring works by Winslow Homer and Mary Cassatt, among others.