Stay in the center, full stop
For a two- or three-day trip there is really one answer: the Centro Histórico. Everything you came for is inside it, it is where the city feels safest and most alive at night, and basing anywhere else means commuting past parts of town that hold no interest. The only real trade-off is hills and cobbles, which matter if you have mobility issues or heavy bags. Prices are a genuine bargain compared with San Miguel de Allende or Guanajuato, because Zacatecas draws a fraction of the crowds. Below are the pockets within the center and who each suits.
Avenida Hidalgo and the cathedral
The heart of it, and the pick for first-timers. Base here and you step straight out into the cathedral, Mercado González Ortega, restaurants and the mezcal bars within a few minutes on foot. Landmarks to picture: the cathedral itself and Plaza de Armas across from the old government palace. Lodging is mostly converted colonial buildings, some grand with courtyards, some creaky and full of character. The trade-off is a bit of night noise on the busier stretches near the bars. Mid-range boutique hotels here run roughly 1,300 to 2,600 MXN a night (approximate), with a couple of grander historic hotels above that.
The quieter upper callejones
Climb a few blocks off Hidalgo, toward the streets below Cerro del Grillo, and the noise drops away fast. Small guesthouses and boutique places up here suit couples and anyone who wants calm at night, with the center still a short walk downhill. The catch is exactly that walk: coming back up at 2,400 meters after dinner and a few mezcales is real exercise. Rooms here span budget guesthouse to mid-range boutique, roughly 900 to 2,000 MXN (approximate).
Budget and backpacker
There are hostels and simple posadas in and just around the center, with dorm beds and basic private rooms at the low end, roughly 300 to 800 MXN (approximate). Book something walkable to Hidalgo rather than chasing a slightly cheaper room out toward the ring road. A useful reference point: anything within a few minutes of Mercado González Ortega puts you in the middle of the food and the mezcal without a taxi.
Families and quiet
Families do best in a courtyard hotel a block or two off the busiest bar streets, near the Alameda or the museum blocks around Museo Rafael Coronel, where you get space and calm at night but stay walkable to the sights. Expect mid-range family-friendly hotels roughly in the 1,400 to 2,800 MXN range (approximate).
What a friend who lives here would tell you
Don’t book by the Central Camionera bus terminal or out on the ring roads to save a few pesos. The center is compact, affordable and the entire reason you came, so pay to be inside it and walk everywhere. If stairs are a problem, ask specifically for a hotel on or just off Hidalgo rather than up in the callejones, and confirm there is no long climb from the street to reception. For why staying central also matters for safety, see is it safe, and for getting from the airport or terminal to your hotel, getting there and around.