Born at Harenkarspel in the Netherlands, Kuiper studied at the University of Leiden, where he obtained his BSc in 1927 and his PhD in 1933. He immediately emigrated to America where he took up an appointment at the Lick Observatory in California and then lectured (1935–36) at Harvard. In 1936 he joined the Yerkes Observatory and in 1939 moved to the McDonald Observatory in Texas, both run by the University of Chicago. He served as their director (1947–49, 1957–60) and was also professor of astronomy (1943–60). From 1960 to 1973 he was head of the Lunar and Planetary Laboratory of the University of Arizona.

Kuiper's main research work was on the solar system. He discovered two new satellites: Miranda, the fifth Uranian satellite in 1948 and Nereid, the second Neptunian satellite in 1949. He also investigated planetary atmospheres and succeeded in detecting carbon dioxide in the Martian atmosphere in 1948. Four years earlier he had found evidence of methane in the atmosphere of Saturn's largest satellite, Titan.

In 1950 he produced some intriguing data on Pluto. Based on observations made with the 200-inch (5-m) reflector at the Palomar Observatory he estimated the diameter of Pluto as 0.23 seconds of arc, which was equivalent to about 3600 miles (5800 km) or half the Earth's diameter. But as its mass was supposed to be roughly the same as that of the Earth it implied the unlikely conclusion that Pluto had a density of about ten times that of the Earth. Recent measurements, however, reveal that Pluto's mass is only 0.2% and its diameter roughly a quarter (2377 km) of Earth's. Kuiper also speculated on the origin of the planets and proposed in 1949 his theory that each planet evolved from its own gaseous cloud that was not initially part of the Sun. This is not generally accepted.

With the advent of the space age, Kuiper became closely involved with several space missions, including the Ranger program, 1961–65, in which the first close-up photographs of the Moon were obtained, and the Mariner 10 flight to Venus and Mercury, which was launched in 1973 shortly before his death.