Louis Kahn, whose original name was Itze-Leib (Leiser-Itze) Schmuilowsky (Schmalowski), was born into a poor Jewish family in Pärnu and spent the rest of his early childhood in Kuressaare on the Estonian island of Saaremaa, then part of the Russian Empire. At age 3, he saw coals in the stove and was captivated by the light of the coal. He put the coal in an apron which later seared his face; he carried these scars for the rest of his life. In 1906, his family immigrated to the United States, fearing that his father would be recalled into the military during the Russo - Japanese War. His actual birth year may have been inaccurately recorded in the process of immigration. According to his son's documentary film in 2003 the family couldn't afford pencils but made their own charcoal sticks from burnt twigs so that Louis could earn a little money from drawings and later by playing piano to accompany silent movies. He became a naturalized citizen on May 15, 1914. His father changed their name in 1915.

He trained in a rigorous Beaux-Arts tradition, with its emphasis on drawing, at the University of Pennsylvania. After completing his Bachelor of Architecture in 1924, Kahn worked as senior draftsman in the office of City Architect John Molitor. In this capacity, he worked on the design for the 1926 Sesquicentennial Exposition.

In 1928, Kahn made a European tour and took a particular interest in the medieval walled city of Carcassonne, France, and the castles of Scotland rather than any of the strongholds of classicism or modernism. After returning to the States in 1929, Kahn worked in the offices of Paul Philippe Cret, his former studio critic at the University of Pennsylvania, and in the offices of Zantzinger, Borie and Medary in Philadelphia. In 1932, Kahn and Dominique Berninger founded the Architectural Research Group, whose members were interested in the populist social agenda and new aesthetics of the European avant-gardes. Among the projects Kahn worked on during this collaboration are unbuilt schemes for public housing that had originally been presented to the Public Works Administration.

Among the more important of Kahn's early collaborations was with George Howe. Kahn worked with Howe in late 1930s on projects for the Philadelphia Housing Authority and again in 1940, along with German born architect Oscar Stonorov for the design of housing developments in other parts of Pennsylvania.

Kahn did not find his distinctive architectural style until he was in his fifties. Initially working in a fairly orthodox version of the International Style, a stay at the American Academy in Rome in the early 1950s marked a turning point in Kahn's career. The back-to-the-basics approach he adopted after visiting the ruins of ancient buildings in Italy, Greece, and Egypt helped him to develop his own style of architecture influenced by earlier modern movements but not limited by their sometimes dogmatic ideologies.

In 1961 he received a grant from the Graham Foundation for Advanced Studies in the Fine Arts to study traffic movement in Philadelphia and create a proposal for a viaduct system. He describes this proposal at a lecture given in 1962 at the International Design Conference in Aspen, Colorado:

In the center of town the streets should become buildings. This should be interplayed with a sense of movement which does not tax local streets for non-local traffic. There should be a system of viaducts which encase an area which can reclaim the local streets for their own use, and it should be made so this viaduct has a ground floor of shops and usable area. A model which I did for the Graham Foundation recently, and which I presented to Mr. Entenza, showed the scheme.

Kahn's teaching career began at Yale University in 1947, and he was eventually named Albert F. Bemis Professor of Architecture and Planning at Massachusetts Institute of Technology in 1962 and Paul Philippe Cret Professor of Architecture at the University of Pennsylvania in 1966 and was also a Visiting Lecturer at Princeton University from 1961 to 1967. Kahn was elected a Fellow in the American Institute of Architects (AIA) in 1953. He was made a member of the National Institute of Arts and Letters in 1964. He was awarded the Frank P. Brown Medal in 1964. He was made a member of the American Academy of Arts and Sciences in 1968 and awarded the AIA Gold Medal, the highest award given by the AIA, in 1971 and the Royal Gold Medal by the RIBA in 1972.

In 1974, Kahn died of a heart attack in a men's restroom in Pennsylvania Station in New York. He went unidentified for three days because he had crossed out the home address on his passport. He had just returned from a work trip to Bangladesh, and despite his long career, he was deeply in debt when he died.

Kahn had three different families with three different women: his wife, Esther, whom he married in 1930; Anne Tyng, who began her working collaboration and personal relationship with Kahn in 1945; and Harriet Pattison. His obituary in the New York Times, written by Paul Goldberger, mentions only Esther and his daughter by her as survivors. But in 2003, Kahn's son with Pattison, Nathaniel Kahn, released an Oscar nominated biographical documentary about his father, titled My Architect: A Son's Journey, which gives glimpses of the architecture while focusing on talking to the people who knew him: family, friends, and colleagues. It includes interviews with renowned architect contemporaries such as B.V. Doshi, Frank Gehry, Ed Bacon, Philip Johnson, I.M. Pei, and Robert A.M. Stern, but also an insider's view of Kahn's unusual family arrangements. The unusual manner of his death is used as a point of departure and a metaphor for Kahn's "nomadic" life in the film.

• Yale University Art Gallery, New Haven, Connecticut,(1951 – 1953), the first significant commission of Louis Kahn and his first masterpiece, replete with technical innovations. For example, he designed a hollow concrete tetrahedral space frame that did away with the need for ductwork and reduced the floor-to-floor height by channeling air through the structure itself. Like many of Kahn's buildings, the Art Gallery makes subtle references to its context while overtly rejecting any historical style.
• Richards Medical Research Laboratories, University of Pennsylvania, Philadelphia, Pennsylvania, (1957 – 1965), regarding which Kahn said, “No space you can devise can satisfy these requirements. I thought what they should have was a corner for thought, in a word, a studio instead of slices of space.”
• The Salk Institute, La Jolla, California, (1959 – 1965), was to be a campus composed of three main clusters: meeting and conference areas, living quarters, and laboratories. Only the laboratory cluster, consisting of two parallel blocks enclosing a water garden, was actually built. The two laboratory blocks frame an exquisite view of the Pacific Ocean, accentuated by a thin linear fountain that seems to reach for the horizon.
• First Unitarian Church, Rochester, New York (1959 – 1969), named as one of the greatest religious structures of the 20th century by Paul Goldberger, Pulitzer Prize winning architectural critic. Tall, narrow window recesses create an irregular rhythm of shadows on the exterior while four light towers flood the sanctuary walls with indirect natural light.
• Indian Institute of Management, Ahmedabad, in Ahmedabad, India (1962).
• Jatiyo Sangshad Bhaban (National Assembly Building) in Dhaka, Bangladesh (1962 – 1974), considered to be his masterpiece and one of the great monuments of International Modernism.
• Phillips Exeter Academy Library, Exeter, New Hampshire, (1965 – 1972), awarded the Twenty-five Year Award by the American Institute of Architects in 1997. It is famous for its dramatic atrium with enormous circular openings into the book stacks.
• Kimbell Art Museum, Fort Worth, Texas, (1967 – 1972), features repeated bays of cycloid shaped barrel vaults with light slits along the apex, which bathe the artwork on display in an ever-changing diffuse light.
• Yale Center for British Art, Yale University, New Haven, Connecticut, (1969 – 1974).
• Franklin D. Roosevelt Four Freedoms Park, Roosevelt Island, New York, (1972 – 1974), unbuilt.

Louis Kahn's work infused the International style with a fastidious, highly personal taste, a poetry of light. His few projects reflect his deep personal involvement with each. Isamu Noguchi called him "a philosopher among architects." He was known for his ability to create monumental architecture that responded to the human scale. He was also concerned with creating strong formal distinctions between served spaces and servant spaces. What he meant by servant spaces was not spaces for servants, but rather spaces that serve other spaces, such as stairwells, corridors, restrooms, or any other back-of-house function like storage space or mechanical rooms. His palette of materials tended toward heavily textured brick and bare concrete, the textures often reinforced by juxtaposition to highly refined surfaces such as travertine marble.

While widely known for his spaces' poetic sensibilities, Kahn also worked closely with engineers and contractors on his buildings. The results were often technically innovative and highly refined. In addition to the influence Kahn's more well known work has on contemporary architects (such as Mazharul Islam, Tadao Ando), some of his work (especially the unbuilt City Tower Project) became very influential among the high-tech architects of the late 20th century (such as Renzo Piano, who worked in Kahn's office, Richard Rogers and Norman Foster). His prominent apprentices include Mazharul Islam, Moshe Safdie, Robert Venturi, Jack Diamond.

Many years after his death, Kahn continues to inspire controversy. Interest is growing in a plan to build a Kahn designed Franklin D. Roosevelt Four Freedoms Park at the southern tip of Roosevelt Island. A New York Times editorial opined:

There's a magic to the project. That the task is daunting makes it worthy of the man it honors, who guided the nation through the Depression, the New Deal and a world war. As for Mr. Kahn, he died in 1974, as he passed alone through New York's Penn Station. In his briefcase were renderings of the memorial, his last completed plan.

The editorial describes Kahn's plan as:

...simple and elegant. Drawing inspiration from Roosevelt's defense of the Four Freedoms – of speech and religion, and from want and fear – he designed an open 'room and a garden' at the bottom of the island. Trees on either side form a 'V' defining a green space, and leading to a two-walled stone room at the water's edge that frames the United Nations and the rest of the skyline.

Critics note that the panoramic view of Manhattan and the UN are actually blocked by the walls of that room and by the trees. Other as-yet-unanswered critics have argued more broadly that not enough thought has been given to what visitors to the memorial would actually be able to do at the site. The proposed project is opposed by a majority of island residents who were surveyed by the Trust for Public Land, a national land conservation group currently working extensively on the island.

The movement for the memorial, which was conceived by Kahn's firm almost 35 years ago, needed to raise $40 million by the end of 2007; as of July 20, it had collected $5.1 million. There is a merest hint in Architectural Record about the often-heard argument that it must be built because it was literally Kahn's last project; and this is rebutted by those who've said the plans aren't enough like Kahn's other work for it to be touted as a memorial to Kahn as well as FDR.