Borzage's father, Luigi, was born in Roncone, Austria-Hungary in 1859. As a stone mason, he sometimes worked in Switzerland; he met his future wife, Maria Ruegg (1860, Ricken - 1947), in Zürich, where she worked in a silk factory. Luigi Borzaga immigrated to Hazleton, Pennsylvania in the early 1880s; he worked as a coal miner there and soon brought his Swiss fiancée with him.
The couple married in Hazleton in 1883, and had their first child, Henry, in Wyoming in 1885. They settled in the Mormon stronghold of Salt Lake City, Utah, where they gave birth to Frank, and remained until 1919. Altogether, the couple had fourteen children, eight of whom survived childhood: Henry (1885-1971), Mary, Bill (1892-1973), Frank, Daniel (1896-1975, a performer and member of the John Ford Stock Company), Lew (1898-1974), Dolly (1901) and Susan (1905). Luigi Borzaga died in Los Angeles in a car accident in 1934; his wife died of cancer in 1947.
Borzage started working in Hollywood in 1912 as an actor, and continued until 1917. His directorial debut came in 1915 with his film The Pitch o' Chance.
On June 7, 1916, Borzage married vaudeville and film actress Lorena "Rena" B. Rogers in Los Angeles. Although he loved her and treated her well, he and his wife were not compatible: she preferred parties, luxury, and travel, while he was less social, except in his athletic activities. Furthermore, Rena secretly had an abortion around 1921— Borzage loved children—and had several female lovers. Despite their common affection, Rena became dissatisfied with her husband, who, according to family members, had discreet affairs with Lupe Vélez, Mary Pickford, Marion Davies, Joan Crawford, and Hedy Lamarr. By 1940 the strain on their marriage had become too great. At a double celebration for Rena's birthday and their anniversary on June 7, Borzage, who then had a drinking problem, suddenly left his mansion and moved out. A divorce was granted on January 22, 1941; Rena obtained $250,000 in damages and interest. Despite this, the couple maintained contact.
Borzage was a successful director throughout the 1920s but reached his peak in the late silent and early sound era. Absorbing visual influences from the German director F.W. Murnau, who was also resident at Fox at this time, he developed his own style of lushly visual romanticism in a hugely successful series of films starring Janet Gaynor and Charles Farrell, including Seventh Heaven (1927), for which he won the first Academy Award for Directing, Street Angel (1928) and Lucky Star (1929). (He won a second Oscar for 1931's Bad Girl.) Borzage's trademark was intense identification with the feelings of young lovers in the face of adversity, love in his films triumphing over such trials as World War I (Seventh Heaven and A Farewell to Arms (1932)), disability (Lucky Star), the Depression (Man's Castle (1933)), a thinly-disguised version of the Titanic disaster in History Is Made at Night (1937), and the rise of Nazism, a theme which Borzage had virtually to himself among Hollywood filmmakers from Little Man, What Now? (1933) to Three Comrades (1938) and The Mortal Storm (1940). His work after 1940, however, took a turn into religiosity in such films as Strange Cargo (1940) and The Big Fisherman (1959), and his once extremely high reputation fell as his earlier films became hard to see; of his later work only the film noir Moonrise (1948) has enjoyed much critical acclaim. After 1948, his output was sporadic, and his last film work was sequences in Edgar G. Ulmer's 1962 film L'Atlantide (Journey Beneath The Desert), for which he was uncredited.
Borzage died of cancer in 1962 at the age of 68, and was interred in the Forest Lawn Memorial Park Cemetery in Glendale, California. For his contributions to film, Borzage was awarded a star on the Hollywood Walk of Fame.