The university is in Heidelberg, one of the larger cities in the state of Baden-Württemberg in the south west of Germany. The nearest international airports are Frankfurt and Stuttgart. A well-connected network of trains and buses runs throughout the state. The university's larger campus, home to many of the institution's biomedical facilities, is in Neuenheimer Feld, to the north of the river Rhine that runs through Heidelberg. The older campus, built around Universitätsplatz (University Square), is on the eastern side of Heidelberg. The university library has buildings on both campuses. It also has clinics in the nearby city of Mannheim.

Heidelberg is a city with approximately 140,000 inhabitants. It is situated in the Rhine Neckar Triangle, a European metropolitan area with approximately 2.4 million people living there, comprising the neighboring cities of Heidelberg, Mannheim, Ludwigshafen, and a number of smaller towns in the perimeter. Heidelberg is known as the cradle of Romanticism, and its old town and castle are among the most frequented tourist destinations in Germany. Its pedestrian zone is a shopping and night life magnet for the surrounding area and beyond. Heidelberg is about 40 minutes by train away from Frankfurt International Airport. Heidelberg University's facilities are, generally speaking, separated in two parts. The faculties and institutes of humanities and social sciences are embedded in the Old Town Campus. The sciences faculties and the medical school, including three large university hospitals, are located on the New Campus in the Neuenheimer Feld on the outskirts of Heidelberg.

Demand for housing in Heidelberg is high and students may find it difficult to secure lodgings. The university does not guarantee accommodation and only about 13% of students are placed in student residences through the university. Nearly half of these are international students. There are several organisations operating in Heidelberg that provide accommodation to students, including Studentenwerk. Lodging in the city centre is significantly more expensive than in the surrounding countryside. Even student accommodation in the centre could cost up to £515 a month (€600).