Centro Histórico: the base most travellers should book
The historic centre of Zacatecas is a UNESCO-listed grid of pink cantera stone that folds into a ravine, and staying inside it puts the cathedral, the Calderón Theatre and the Santo Domingo church within a ten-minute walk. Hotels cluster on Avenida Hidalgo, Calle Tacuba and the streets off Plaza de Armas. Expect small colonial properties with interior courtyards, thick walls and rooms that stay cool without air conditioning; ask about heating if you travel in December or January, when nights near 2,000 metres altitude drop close to freezing.
Parking is the practical dividing line. Many centro hotels have no garage and the streets around Plaza de Armas are narrow and one-way, so if you arrive by car confirm a space before booking or plan to use a public lot near Avenida González Ortega. For a first visit of two or three nights, this is the area I would book: you can walk to dinner, hear the cathedral bells, and skip taxis entirely for the main sights.
Cerro de la Bufa and the hillside
La Bufa is the rocky outcrop east of the centre, crowned by the Ex-convento and the cable car station, with the Mina El Edén entrance a short walk downhill. Hotels along the access road and near the Buffa viewpoint trade convenience for views; the payoff is the panorama over the city at dusk, when the stone turns amber. The trade-off is distance: it is a steep 20-to-25-minute walk down into the centre and a lung-testing climb back, or a short, cheap taxi ride.
If you are travelling for the cable car, the mine and the viewpoint, two nights up here is pleasant, but I would not make it a whole trip's base. The road up is dark after dinner and few restaurants sit within walking distance. Book hillside only if you have a car or do not mind relying on taxis, and check that the room has heating in winter and reliable hot water.
Quiet streets: Guadalupe and the northern edge
Guadalupe, the former colonial town now joined to Zacatecas, holds the Museo de Guadalupe with its extraordinary painted ceilings and cloister, and the streets around Calle García Salinas are calm, flat and lined with low buildings. It is around 10 to 15 minutes by taxi from the centro, or a straightforward local bus ride, and hotels here tend to be simpler and quieter than the historic core. This suits travellers with a car, families, or anyone who wants to sleep without bar noise.
The catch is that Guadalupe has fewer places to eat in the evening and you will be travelling into the centre for the cathedral, the mine and the museums. I would use it for a restful final night before an early flight or bus, rather than for the whole stay. Check the exact address against the Museo de Guadalupe, because the boundary with Zacatecas city is not obvious on the ground.
When to go and how to choose
The dry months from October to April are the most comfortable, with clear skies and cool nights; May and June heat up before the rains arrive in July and August, when afternoon storms are common. The Feria Nacional de Zacatecas in September fills the city and pushes room rates up, so book well ahead then. Weekends are busier than weekdays, and the centro's main plazas host evening events that can be noisy late into the night.
Match the area to your trip rather than the other way round: centro for a first visit and walkability, Bufa for views and the cable car, Guadalupe for quiet and a car. Cross-check a hotel's exact street on a map before booking so you know the climb back from the plaza. Our own search data shows centro properties draw the most interest in Zacatecas, which is a fair signal of where most travellers end up, but not a rule.