A writer zooms down the Autostrada from Rome for a few days in Puglia and has one of the best gastronomic weekends of her life.

I was sipping walnut liqueur at an old café in the obscure Italian town of Altamura when I realized that, in the middle of nowhere, I'd just had one of the best food days of my life. And I had figured out why stylish Romans are spending their weekends in Puglia, the formerly destitute but agriculturally rich region in southern Italy. They escape here to explore the beaches and country roads, meandering past vineyards and silvery olive groves to sample Italy's most Mediterranean cooking and to stock up on the boutique olive oils, wines and pickles that testify to the region's gastronomic emergence.

That walnut liqueur capped off an idyllic weekend in Puglia. My friend and I saw the region's most enchanting towns, best restaurants and loveliest whitewashed hotels—and made sure to leave plenty of time to eat.

Day 1

We left Rome early on a Friday morning, zooming down the autostrada. Five hours later, we sat down to tiny squid with an iridescent arugula puree at the elegant vaulted dining room of Ristorante Bufi, renowned for its seafood, in the historic fishing port of Molfetta, west of Bari. We followed it with tender cuttlefish slivers sandwiched between baked eggplant slices, and marmora, an oily fish, offset by fried uncured nolche olives. The olives burst like bittersweet grapes when you bite into them—that dish alone was worth the drive from Rome.

With dessert on our minds, we headed south to Polignano a Mare, Puglia's ice cream mecca. The beauty of the town, bisected by a dramatic ravine that leads to the sea, was an unwelcome distraction: We were interested only in Il Super Mago del Gelo ice cream shop, justly venerated for its fruit gelati and dark, slushy coffee granita. We sampled fig, lemon and the astounding caffè-nocciola gelato, and then sped off.

It was getting dark when we found Il Frantoio, a farm with an inn near Ostuni, off a cyprus-lined road parallel to the sea. Expecting a modest agriturismo, we encountered a little agricultural utopia, centered around a masseria (a traditional fortified farmhouse) hidden by olive trees and flanked by a citrus grove. There's something unsettlingly perfect about the world of Armando Balestrazzi and Rosalba Ciannamea, the couple who own the place. I ambled around the grounds wondering how the horses, even the chickens, could be so exquisite, the inn's antiques so impeccably tasteful and the peppers and figs in the cellar so unblemished and ripe.

While the tireless Balestrazzi—a man who traded his high-ranking post at a big dairy company for inn-keeping and organic farming—tends to the guests, Ciannamea masterminds improbably lovely 10-course dinners with ingredients from the farm. For our meal, she garnished smoked mozzarella with tiny clover bouquets, topped herb pasta with a luxurious saffron sauce and doused fried lampascioni (wild hyacinth bulbs) with orange-blossom honey.

Day 2

The next morning we inspected the inn's antique olive press, once used to produce blond, fruity oils (they're now pressed a few miles away). Puglian olives supply Italy with nearly half its oil, but what was formerly plonk for blending is now competing with top bottles from Tuscany and Liguria. Low in acidity, Il Frantoio's oils were as refined as anything I'd tasted up north.

Olives aside, Puglia's greatest draw is architecture: Romanesque, Gothic, Baroque and those whitewashed Greek-style villages that recall the Aegean (Puglia was part of Magna Graecia, or greater Greece, for several centuries). Still, most Italians come here to gawk at the trulli, the ancient cylindrical limestone houses capped by conical stone roofs.

Our Fiat weighed down with Il Frantoio's olive oils and mulberry and pomegranate liqueurs, we headed inland to Alberobello, the epicenter of trulli-tourism, with some 1,500 of these fairy-tale huts crowding the hills and town center. Alberobello would have been adorable, if not for the souvenir shops and tour buses. I had to admire the old nonne in black who knit outside their Lilliputian dwellings, impervious to the Japanese camera flashes.

Our lunch destination was the Michelin-starred Al Fornello da Ricci in Ceglie Messapica, where a young chef, Antonella Ricci, cooks alongside her mother, Dora, and her Mauritian husband, Vinod Sokar. A beamed farmhouse with lamps fashioned from copper buckets and long tables crowded with families, Al Fornello seemed like the Platonic ideal of an Italian country restaurant—until a cherubic five-year-old crashed into my expensive bottle of Donna Lisa Riserva. I must have been a sight: drenched purple-red and encircled by the child's dozen relatives who simultaneously rubbed salt all over my clothes and smothered the offender with kisses. My consolation was Antonella's soufflé-like spinach omelet and zucchini-blossom fritters filled with sheep's-milk ricotta, followed by Dora's grano (fat wheat kernels with a rich meat ragù). To finish, there was grappa and almond-cherry biscotti in the restaurant's garden, replete with its own trullo. But the five-year-old struck again—ripping a page of crucial phone numbers from my book and sending it flying.

After a half-hour drive, we relaxed at Masseria San Domenico, near Fasano, a five-star resort with 150 acres of grounds, a vast saltwater pool and rooms outfitted with Frette linens. No one in Italy would contemplate dinner after a huge weekend lunch, so, following more grappa at the bar, we retired to our room.

Day 3

San Domenico's thalassotherapy (seawater) spa deserved a whole day. But lunch awaited us in the town of Gravina in Puglia, in the rocky Murgia highlands. Neotraditional Osteria di Salvatore Cucco wouldn't be out of place in Manhattan, except that the limestone and the wines are produced nearby. The Puglian genius for preserving showed in our antipasti of pickled baby tomatoes and peppers, and artichokes marinated in lemony oil. Up next were orecchiette deliciously sauced with cicerchie (like a cross between garbanzo and fava beans) and cardoncelli, the delicate musky wild mushrooms that locals adore. The cheeses amounted to a regional tour: stringy, braided baby mozzarella, a tub of pungent aged ricotta and the greatest Puglian cheese, burrata, a mozzarella-like sack filled with curds and rich cream.

Admiring the fruity-sweet, young Botromagno Primitivo, we chatted up the winery's owners, who were lunching at the next table. While their reds are successful locally, Alberto and Beniamino D'Agostino, two young brothers, are mostly acclaimed as the only producers of Gravina D.O.C., a bright white with a faint aroma of apples. One of Italy's largest wine regions, Puglia is graduating from bulk wines to worldly bottlings that are earning tre bicchieri (three glasses), the highest prize, from the influential Gambero Rosso guide. The D'Agostinos, however, aren't growing lucrative foreign varietals, preferring to stay true to the area with elegant wines based on indigenous grapes.

It was sheer gluttony that led us to the nearby hill town of Altamura, renowned for its stocky 800-year-old Romanesque-Gothic cathedral and for its bread. Made with natural leavening and durum wheat, pane di Altamura is left to rise three times, shaped into vast rugged loaves and baked in wood-fired ovens at bakeries all over town.

We bought a loaf almost the size of a car tire and took it to the weathered marble counter at Caffè Ronchi, where the barrista introduced us to the miraculous walnut liqueur called Padre Peppe Nocino. We sipped the viscous, bracingly bitter liquid, cataloging the incredible things we'd eaten and drunk over the weekend. One question remained: What did that spilled Donna Lisa Riserva actually taste like?

Anya von Bremzen is the author of four cookbooks, including The Greatest Dishes! Around the World in 80 Recipes.