Cairo is located in northern Egypt, known as Lower Egypt, 165 kilometers (100 mi) south of the Mediterranean Sea and 120 kilometers (75 mi) west of the Gulf of Suez and Suez Canal. The city is along the Nile River, immediately south of the point where the river leaves its desert-bound valley and branches into the low-lying Nile Delta region. Although the Cairo metropolis extends away from the Nile in all directions, the city of Cairo resides only on the east bank of the river and two islands within it on a total area of 214 square kilometers (83 sq mi).

Until the mid-19th century, when the river was tamed by dams, levees, and other controls, the Nile in the vicinity of Cairo was highly susceptible to changes in course and surface level. Over the years, the Nile gradually shifted westward, providing the site between the eastern edge of the river and the Mokattam highlands on which the city now stands. The land on which Cairo was established in 969 (present-day Islamic Cairo) was located underwater just over three hundred years earlier, when Fustat was first built.

Low periods of the Nile during the 11th century continued to add to the landscape of Cairo; a new island, known as Geziret al-Fil, first appeared in 1174, but eventually became connected to the mainland. Today, the site of Geziret al-Fil is occupied by the Shubra district. The low periods created another island at the turn of the 14th century that now composes Zamalek and Gezira. Land reclamation efforts by the Mamluks and Ottomans further contributed to expansion on the east bank of the river

Because of the Nile's movement, the newer parts of the city - Garden City, Downtown Cairo, and Zamalek - are located closest to the riverbank. The areas, which are home to most of Cairo's embassies, are surrounded on the north, east, and south by the older parts of the city. Old Cairo, located south of the center, holds the remnants of Fustat and the heart of Egypt's Coptic Christian community, Coptic Cairo. The Boulaq district, which lies in the northern part of the city, was born out of a major 16th-century port and is now a major industrial center. The Citadel is located east of the city center around Islamic Cairo, which dates back to the Fatimid era and the foundation of Cairo. While western Cairo is dominated by wide boulevards, open spaces, and modern architecture of European influence, the eastern half, having grown haphazardly over the centuries, is dominated by small lanes, crowded tenements, and Islamic architecture.

Northern and extreme eastern parts of Cairo, which include satellite towns, are among the most recent additions to the city, as they developed in the late-20th and early-21st centuries to accommodate the city's rapid growth. The western bank of the Nile is commonly included within the urban area of Cairo, but it composes the city of Giza and the Giza Governorate. Giza has also undergone significant expansion over recent years, and today the city, although still a suburb of Cairo, has a population of 2.7 million. The Cairo Governorate is just north of the Helwan Governorate, which was created in 2008 when some of Cairo's southern districts, including Maadi and New Cairo, were split off and annexed into the new governorate