Rossellini was born in Rome. His mother, Elettra (née Bellan), was a housewife born in Rovigo, Veneto, and his father, Angiolo Giuseppe "Beppino" Rossellini, who owned a construction firm, was born in Rome from a family originally from Pisa, Tuscany. His mother was of part French descent, from immigrants who had arrived in Italy during the Napoleonic Wars. He lived on the Via Ludovisi, where Benito Mussolini had his first Roman hotel in 1922 when Fascism obtained power in Italy.
Rossellini's father built the first cinema in Rome, the "Barberini", a theater where movies could be projected, granting his son an unlimited free pass; the young Rossellini started frequenting the cinema at an early age. When his father died, he worked as a soundmaker for films and for a certain time he experienced all the ancillary jobs related to the creation of a film, gaining competence in each field. Rossellini had a brother, Renzo, who later scored many of his films.
On 26 September 1936, he married Marcella De Marchis (17 January 1916, Rome – 25 February 2009, Sarteano), a costume designer with whom he collaborated even after their marriage was over. This was after a quick annulment from Assia Noris, a Russian actress who worked in Italian films. De Marchis and Rossellini had two sons: Marco Romano (born 3 July 1937 and died of appendicitis in 1946), and Renzo. Rossellini and De Marchis separated in 1950 (and eventually divorced). He later married a Bengali screen-writer, Sonali Dasgupta nee Senroy. They raised their son Gil in Italy, who was adopted by Roberto and is now a New York-based film producer and had one daughter, Raffaella Rossellini, together. Although he wasn't personally religious, he had a strong interest in Christian values in the contemporary world; he loved the Church's ethical teaching, and was enchanted by religious sentiment—things which he saw as being neglected in the materialist world.
In 1937, Rossellini made his first documentary, Prélude à l'après-midi d'un faune. After this essay, he was called to assist Goffredo Alessandrini in making Luciano Serra pilota, one of the most successful Italian films of the first half of the 20th century. In 1940 he was called to assist Francesco De Robertis on Uomini sul Fondo. His close friendship with Vittorio Mussolini, son of Il Duce, has been interpreted as a possible reason for having been preferred to other apprentices.
Some authors describe the first part of his career as a sequence of trilogies. His first feature film, The White Ship (1941) was sponsored by the audiovisual propaganda centre of Navy Department and is the first work in Rossellini's "Fascist Trilogy", together with A Pilot Returns (1942) and The Man with a Cross (1943). To this period belongs his friendship and cooperation with Federico Fellini and Aldo Fabrizi. The Fascist regime collapsed in 1943 and just two months after the liberation of Rome (4 June 1944), Rossellini was already preparing the anti-fascist Roma città aperta (Rome, Open City 1945). Fellini assisted on the script and Fabrizi played the role of the priest, while Rossellini self-produced. Most of the money came from credits and loans, and film had to be found on the black market. This dramatic film was an immediate success. Rossellini had started now his so-called Neorealistic Trilogy, the second title of which was Paisà (1946), produced with non-professional actors, and the third, Germany, Year Zero (1948), sponsored by a French producer and filmed in Berlin's French sector. In Berlin also, Rossellini preferred non-actors, but he was unable to find a face he found "interesting"; he placed his camera in the center of a town square, as he did for Paisà, but was surprised when nobody came to watch.