Hyderabad is 164 km north of Karachi by the Indus Highway (M9 motorway) — approximately 2 hours by bus or car. The Karachi–Peshawar Railway Line passes through Hyderabad Junction station, with multiple trains daily between the two cities. The bus station and railway station are both in the south of the city near the Indus River.
From Hyderabad, buses and wagons connect to Sukkur (about 3 hours north), Larkana, and smaller Sindhi towns. For travellers heading to the interior of Sindh — Mohenjo-Daro, Sukkur, or the Thar Desert — Hyderabad is the natural first overnight stop.