A community of interests had already existed between Bayer, BASF and Agfa since 1905. In order to regain access to the vital export markets, these and other companies of the German tar dyes industry joined together in a larger community of interests in 1915/16 on the initiative of Carl Duisberg.

Once the global economy stabilized in the mid-20s, it became clear that the German dyestuffs industry would be unable to regain its old position in the world market. In order to remain competitive and gain access to new markets, the companies belonging to the community of interests decided to merge in 1925. Bayer transferred its assets to I.G. Farbenindustrie AG (I.G.) and was deleted from the commercial register as a company.
Yet the Bayer tradition lived on in the I.G.'s Lower Rhine operating consortium, which consisted of the Leverkusen, Dormagen and Elberfeld sites, as well as the Uerdingen site. Leverkusen also became the headquarters for the I.G.'s pharmaceutical sales association, and the Bayer Cross was used as the trademark for all of the I.G.'s pharmaceutical products.

Within the network of I.G. sites, Leverkusen also developed into a key production location for basic chemicals and intermediates, as well as the largest dyestuffs production site. Rubber synthesis and modern polymer chemistry were the focus of research activities at this time.
In the early 1930s, polyacrylonitrile-butadiene-rubber (Perbunan) was developed here, and Otto Bayer (1902–1982) invented polyurethanes in 1937. The Wupperal-Elberfeld facility continued its successful research into drugs to control malaria. Working together with Fritz Mietzsch (1896–1958) and Joseph Klarer (1898–1953), Gerhard Domagk (1895–1964) discovered the therapeutic effect of the sulfonamides, with one active ingredient from this class of substances being launched in 1935 as Prontosil – a key breakthrough in the chemotherapy of infectious diseases for which Domagk received the Nobel Prize in 1939.

After the recovery between 1926 and 1928, the Great Depression finally reached the Lower Rhine consortium as well. Output and employment declined dramatically. In 1929, the Elberfeld and Leverkusen sites together employed 12,450 people. By July 1932, this number had dropped to only 9,800, so jobs had been cut by 20 percent. Only later in the 1930s did the workforce begin to grow again.

In 1936 the National Socialist government began systematically preparing for war.
When the Second World War finally broke out in 1939, the locations of the Lower Rhine consortium were among the sites of German industry that were considered "vital to the war." Production requirements grew steadily, yet more and more employees were drafted into military service. For this reason, foreign and forced laborers from the occupied countries of Europe were brought to work in Leverkusen, Dormagen, Elberfeld and Uerdingen – and throughout the German industry as a whole – to maintain output levels. At times during the war, these laborers accounted for up to one third of the workforce. Concentration camp prisoners were not employed in the Lower Rhine sites.

For the Leverkusen site, the war ended on April 14, 1945, with the arrival of American troops. As Leverkusen was located in the British occupation zone, the British military government soon assumed complete control over the Lower Rhine sites.