Louis Nathaniel von Rothschild was born in 1882, the third of seven children of Albert Salomon and Bettina Caroline von Rothschild. After completing his schooling at the Theresianum in Vienna, he trained as a bank clerk in Hamburg and New York. He started studying law in Munich, but in keeping with his diverse interests also attended lectures in aesthetics, experimental physics, anthropology and the history of art and culture. In 1907 he joined the board of administrators of the Salomon M. Rothschild bank, founded by his great-grandfather, at Rennstraße 3 in Vienna's 1st district. He was also a member of the board of administrators of the Austrian Creditanstalt für Handel und Gewerbe and from 1922 sat on the General Council of the Austrian National Bank. In 1911, after the death of Albert Rothschild, at his father's request he became sole manager of the family's Vienna bank house and also took over the shares in the Creditanstalt für Handel und Gewerbe in Vienna and the Ungarische Allgemeine Kreditbank in Budapest. His unshakable calmness is frequently mentioned in the literature, and this could well be the reason he was designated as head of the Vienna Rothschild family. The Rothschild bank was linked in addition with industrial concerns such as the Kammgarnfabrik in Vöslau, the Mineralöl-Raffinerie AG in Budapest, the Škoda group and Stabilimento Tecnico Triestino. Louis was also chairman of the board of the ironworks in Witkowitz (Vítkovice) and sole representative for the family mining shares. In 1911 he took over the residence built from 1876 to 1884 by his father at Heugasse 24–26, renamed Prince-Eugen-Straße 20–22 in Vienna's 4th district, together with the extensive art collection. The objects were not displayed in a museum setting like as they were by his brother Alphonse, who in 1905 inherited the residence at Theresianumgasse 16–18 in the 4th district along with Nathaniel Rothschild's art collection. A report in the Neues Wiener Journal on 1 November 1930 described the artworks owned by Louis Rothschild as the "largest private collection of eighteenth-century art" in Vienna, with paintings by Jean-Honoré Fragonard, François Boucher, Thomas Gainsborough and George Romney. The collection consisted of over one thousand items, also including miniatures, watercolours, drawings, furniture, porcelain, clocks and watches, chandeliers, old weapons, sculptures, tapestries and medals from the sixteenth to nineteenth centuries. Louis was also known to be a passionate polo player, outstanding horseman and enthusiastic hunter. He passed the balloon pilot examination and also had a pilot's licence. For a long time he must have been one of the most eligible but also one of the most confirmed bachelors in Viennese high society.

On 12 March 1938, the date of the annexation of Austria to the Nazi German Reich, Louis managed to organize the escape of his nieces Bettina (1924–2012) and Gwendoline (1927–1972). He himself did not escape persecution. He was arrested at Aspern airfield by two SA men and escorted to his residence. The following day he was imprisoned by the Gestapo at the police prison at Rossauer Lände 7–9 and then on the fifth floor of the Gestapo headquarters in Hotel Metropol on Morzinplatz, where he was locked up for fourteen months. On 14 March 1938, the Gestapo sealed both Rothschild residences, leaving the seized art collections in place for the time being. In August of that year, the Central Office for Jewish Emigration moved into the residence on Prinz-Eugen-Straße and from 1942 the Deutsche Reichspost. The S. M. von Rothschild private bank was put under provisional directorship on 26 March 1938. On 8 July it was put in the charge of Merck, Fink & Co, a private bank in Munich. The family bank was later expropriated and ultimately taken over the E. v. Nicolai & Co. bank in Vienna. After Fritz Dworschak, provisional director of the Kunsthistorisches Museum (KHM), was appointed to take charge of the Rothschild art assets in May 1938 and was subsequently commissioned as well to establish the Central Depot for Seized Collections, KHM employees transported Louis Rothschild's art collection on 3 October 1938 to the first floor of the Neue Burg on Heldenplatz in Vienna. The Central Depot catalogue for 1938/39 listed 919 objects (later increased to 964). There was a separate list of 189 medals. File cards probably written later included a further 159 not clearly identifiable items with the abbreviation AALR (Alphonse or Louis Rothschild) and 11 with the abbreviation LR_NB (Louis Rothschild Neue Burg). While a good number of the art objects were reserved for Hitler's planned art museum in Linz, the furnishings were assigned for the most part to the Neue Burg and Palais Pallavicini in Vienna. The remainder was to be distributed successively to other museums, which from late 1938 onwards had submitted extensive wish lists. The family had finally to relinquish title to all remaining assets in return for the Louis Rothschild's release by the Gestapo on 11 May 1939. The official contract of sale of the Witkowitzer Eisenwerke was signed on 13 July 1939 but never implemented, because the majority of the shares had already been transferred before the annexation to Alliance Assurance Ltd., a British trust in London.

After escaping from Europe, Louis Rothschild applied in October 1940 in Buenos Aires for a stateless passport, but did not initially obtain a visa for the USA and was unable to travel to New York until February 1941. He became a US citizen in 1946, married Hilda Auersberg, who had also emigrated from Vienna, and lived with her on a large farm in East Barnard, Vermont. After the war, Czechoslovakia nationalized the ironworks in Vítkovice and in 1953 paid Rothschild a million pounds in compensation. Rothschild ceded his real estate properties in Austria to the State in return for a contractual assurance that it would pay the pensions of all former employees. Not all of the artworks in Louis Rothschild's collection were listed and distributed to museums, as a police investigation from 1947 concerning a former Rothschild employee responsible for the inventory in Prinz-Eugen-Straße demonstrates. He had transferred furniture, pictures and carpets without inventory numbers to his apartment and that of his parents-in-law before the residence was sealed. As was discovered after his suicide, he had attempted to sell the tapestries at least on the art market. The restitution of art objects administered by the State after 1945 was less a matter of chance. In July 1946 with the agreement of the Rothschild family and in preparation for the actual restitutions, the Federal Monuments Authority (BDA) organized the transfer to Palais Springer at Metternichgasse 8 in Vienna's 3rd district of the objects from the Rothschild collections in storage in the Neue Burg and in Steyersberg and Thürnthal. In August 1947 the Federal Ministry for Securing Property and Economic Planning agreed to the release of those objects from the former Linz art museum still stored in the salt mine in Altaussee but ordered the retention of some objects selected for "donation". In September 1947, in return for authorization to export the restituted objects to the USA, Louis Rothschild (and his sister-in-law Clarice) had to give some of his art objects to Austrian museums. The KHM demanded four paintings, sixteen medals and ten old weapons, the Albertina Graphic Art Collection fifteen miniatures, drawings, watercolours and engravings, the Austrian Museum of Applied Arts two small tables and a carpet, the Österreichische Galerie seven paintings, and the Clock Museum three clocks. By virtue of a decision of the Provincial Tax Office for Vienna, Lower Austria and Burgenland (FLD) of 23 September 1947, all objects from Louis Rothschild's collection held by the BDA were to be restituted. The list of objects handed to the trustee Trauttmansdorff on 23 October 1947 was twenty-two pages long, with some corrections and one supplementary page. Around one third of the objects listed by the BDA had no LR number, however, and in view of the sketchy description of these objects it will be almost impossible to identify them for certain. In November 1947, Rothschild's legal representative applied for and received authorization from the BDA to export 186 items to New York, mainly applied art objects along with some paintings and prints, with an estimated total value of 648,300 schillings. A decision on 10 May 1948 by the Federal Ministry for Securing Assets and Economic Planning authorized the release of fourteen items from the Louis Rothschild collection that had been secured in late 1947 and stored in the pan house of the Altaussee salt mine. Further restitutions were authorized by the FLD on 4 June 1948 (nine items from the depot in the Salzburg Residence) and on 3 September that year (forty-four items from the Kunsthistorisches Museum Weapons Collection, stored in the depot at Metternichgasse 8). Restitution decisions were passed on 31 January 1949 for objects from both Rothschild collections from the BDA depots in Altaussee, Kremsmünster and the Salzburg Residence (thirty items to Louis, ten to Clarice Rothschild). On 13 September 1949 the FLD decided that a further six items from the depots at Palais Springer and in the Salzburg Residence should be restituted. Finally, on 12 March 1952 two dragon-head door handles also found in the Salzburg Residence were returned to Rothschild. Further research is required to determine how many objects from Louis Rothschild's collection were returned to him before his untimely death on 15 January 1955 while on holiday in Jamaica, and which of them he kept or sold.

Starting in 1998, seven provenance research dossiers have been established to investigate a total of sixty objects from Louis Rothschild's collection in Austrian federal museums, which were subsequently recommended for restitution. In 2013, the Art Restitution Advisory Board also recommended the return of parts of the Rothschild family archive that had been "donated" to the Austrian State Archives by the Soviet Union in 1960. Thirty-three of the forty-five objects listed in the Art Restitution Advisory Board decision of 11 February 1999 and subsequently restituted were auctioned in July 1999 at Christie's in London. Restitution decisions for Louis Rothschild's descendants were also passed in the provinces. In 1999, the Lower Austria Provincial Museum (now Museum Niederösterreich) restituted a pen drawing by Martin Johann, The Sacrifice of Iphigenia, which had been "donated" to the museum in 1949. A painting, three books and five drawings obtained by the Reichsgaumuseum Niederdonau in 1940 from Louis Rothschild's collections and in storage at the depot in Altenburg Abbey had been designated in 1945 as "lost art", and two pairs of Chinese vases were returned in 1949. In 1999, Museen der Stadt Wien restituted eleven objects to the descendants of Alphonse and Louis Rothschild. In 2000, the Universalmuseum Joanneum in Graz returned A Landscape Study by Herbert Boeckel. In 2008, the Tiroler Landesmuseum Ferdinandeum returned a Portrait of the Senator Adam Rzyszewski by Johann Baptist Lampi the Elder given to it in 1947. In 2019, the board of Salzburg Museum decided to return a round shield given to it in 1941. As the accessibility of important source material has improved in recent years, it is possible that systematic and networked provenance research in Austria will reveal further art objects from the Louis Rothschild collection in the years to come.