He was born in Rotterdam, the son of Hendrik Willem van Loon and Elisabeth Johanna Hanken. He went to the United States in 1902 to study at Cornell University, receiving his degree in 1905. He was a correspondent during the Russian Revolution of 1905 and in Belgium in 1914 at the start of World War I. He later became a professor of history at Cornell University (1915—17) and in 1919 became an American citizen. At Cornell, he was admitted to that university's Irving Literary Society.

In 1906 he married Eliza Ingersoll Bowditch, daughter of a Harvard professor, by whom he had two sons, Henry Bowditch and Gerard Willem. He had two later marriages, to Eliza Helen (Jimmie) Criswell in 1920 and playwright Frances Goodrich Ames in 1927, but after a divorce from Ames he returned to Criswell (it is debatable whether or not they re-married) who inherited his estate in 1944.

From the 1910s until his death, van Loon wrote many books, illustrating them himself. Most widely known among these is The Story of Mankind, a history of the world especially for children, which won the first Newbery Medal in 1922. The book was later updated by van Loon and has continued to be updated, first by his son and later by other historians.

However, he also wrote many other very popular books aimed at young adults. As a writer he was known for emphasizing crucial historical events and giving a complete picture of individual characters, as well as the role of the arts in history. He also had an informal and thought-provoking style which, particularly in The Story of Mankind, included personal anecdotes.

The titles and subtitles of his books are notable for being lengthy.

Asked how to say his name, he told The Literary Digest "I still stick to the Dutch pronunciation of the double o...Loon like loan in 'Loan and Trust Co.' My sons will probably accept the American pronunciation. It really does not matter very much." In fact, three generations later, van Loon's great-grandchildren still use the "loan" pronunciation.

A list of works by Hendrik Willem van Loon, with first publication dates and publishers.

• The Fall of the Dutch Republic, 1913, Houghton Mifflin Co.
• The Rise of the Dutch Kingdom, 1915, Doubleday Page & Co.
• The Golden Book of the Dutch Navigators, 1916, The Century Co.
• A Short History of Discovery: From the Earliest Times to the Founding of Colonies in the American Continent, 1917, David McKay
• Ancient man; the Beginning of Civilizations, 1920, Boni and Liveright
• The Story of Mankind, 1921, Boni and Liveright
• The Story of the Bible, 1923, Boni and Liveright
• Witches and Witch-Finders, 1923, article from the June 1923 Mentor Magazine
• The Story of Wilbur the Hat, 1925, Boni and Liveright
• Tolerance, 1925, Boni and Liveright
• The Liberation of Mankind: the story of man's struggle for the right to think, 1926, Boni and Liveright
• America: The Story of America from the very beginning up to the present, 1927, Boni and Liveright
• Adriaen Block, 1928, Block Hall
• Multiplex man, or the Story of Survival through Invention, 1928, Jonathan Cape
• Life and Times of Peter Stuyvesant, 1928, Henry Holt
• Man the Miracle Maker, 1928, Horace Liveright
• R. v. R.: the Life and Times of Rembrandt van Rijn, 1930, Horace Liveright
• If the Dutch Had Kept Nieuw Amsterdam, in If, Or History Rewritten, edited by J. C. Squire, 1931, Simon and Schuster
• Van Loon's Geography: The Story of the World We Live In, 1932, Simon and Schuster
• "Gold" 1933, article from the Cosmopolitan March 1933
• An Elephant Up a Tree, 1933, Simon and Schuster
• An Indiscreet Itinerary or How the Unconventional Traveler Should See Holland by one who was actually born there and whose name is Hendrik Willem Van loon, 1933, Harcourt, Brace
• The Home of Mankind: the story of the world we live in, 1933, George G. Harrap
• The story of inventions: Man, the Miracle Maker, 1934, Horace Liveright
• Ships: and How They Sailed the Seven Seas (5000 B.C.-A.D.1935), 1935, Simon and Schuster
• Around the World With the Alphabet, 1935, Simon and Schuster
• Air-Storming (radio talk), 1935, Harcourt, Brace
• Love me not, 1935
• A World Divided is a World Lost, 1935, Cosmos Publishing Co.
• The Songs We Sing (with Grace Castagnetta), 1936, Simon and Schuster
• The Arts (with musical illustrations by Grace Castagnetta), 1937, Simon and Schuster
• Christmas Carols (with Grace Castagnetta), 1937, Simon and Schuster
• Observations on the mystery of print and the work of Johann Gutenberg, 1937, Book Manufacturer's Institute/New York Times
• Our Battle: Being One Man's Answer to "My Battle" by Adolf Hitler, 1938, Simon and Schuster
• How to Look at Pictures: a Short History of Painting, 1938, National Committee for Art Appreciation
• Folk Songs of Many Lands (with Grace Castagnetta), 1938, Simon and Schuster
• The Last of the Troubadours: The Life and Music of Carl Michael Bellman 1740-1795 (with Grace Castagnetta), 1939, Simon and Schuster
• The Songs America Sings (with Grace Castagnetta), 1939, Simon and Schuster
• My School Books, 1939, E. I. du Pont de Nemours
• Invasion, being the personal recollections of what happened to our own family and to some of our friends during the first forty-eight hours of that terrible incident in our history which is now known as the great invasion and how we escaped with our lives, 1940, Harcourt, Brace
• The Story of the Pacific, 1940, George G. Harrap
• The Life and Times of Johann Sebastian Bach, 1940, Simon and Schuster
• Good Tidings (with Christmas songs by Grace Castegnetta), 1941, American Artists Group
• The Praise of Folly by Desiderius Erasmus of Rotterdam, with a short life of the Author by Hendrik Willem van Loon of Rotterdam who also illustrated the Book, 1942
• Van Loon's Lives: Being a true and faithful account of a number of highly interesting meetings with certain historical personages, from Confucius and Plato to Voltaire and Thomas Jefferson, about whom we had always felt a great deal of curiosity and who came to us as dinner guests in a bygone year, 1942, Simon and Schuster
• Christmas Songs, 1942
• The Message of the Bells (with music by Grace Castagnetta), 1942, New York Garden City
• Fighters for Freedom: the Life and Times of Thomas Jefferson and Simon Bolivar, 1943, Dodd, Mead & Co.
• The Life and Times of Scipio Fulhaber, Chef de Cuisine, 1943
• Adventures and Escapes of Gustavus Vasa, and how they carried him from his rather obscure origin to the throne of Sweden, 1945
• Report to Saint Peter, upon the kind of world in which Hendrik Willem van Loon spent the first years of his life - an unfinished, posthumously published autobiography, 1947, Simon and Schuster

The Italian songwriter Francesco Guccini has composed a song, dedicated to the memory of hisfather, who was a lover of van Loon's works when he was young. The song is titled "Van Loon", and appears in the album Signora Bovary.