Karl Mayer was initially a partner in the company V. Mayer & Söhne founded by his grandfather and later an industrialist in Vienna. On 3 July 1890 he married Monika von Goldschmidt (1862–1908) and on 8 May 1891 their only son was born. Monika Mayer began to collect porcelain figures and her husband took up her enthusiasm. Seventy porcelain objects from the Wiener Manufaktur were shown publicly for the first time at the exhibition on the Congress of Vienna in 1896 at the k. k. Österreichisches Museum für Kunst und Industrie (Imperial Royal Museum of Art and Industry). After lending sixty items in 1903 for the exhibition of Alt-Wiener porcelain in the Kaiser Franz Josef-Museum für Kunst und Gewerbe in Troppau, he provided 303 items the following year for the exhibition of Alt-Wiener Porcelain at the Österreichisches Museum in Vienna and as such was by far the most important lender. Although he owned other artworks, he specialized in porcelain, and in 1914, Josef Folnesics, curator at the Österreichisches Museum, published Die Wiener-Porzellan-Sammlung Karl Mayer and listed 528 items from the collection. Fourteen years later, Mayer decided to sell the collection, possibly because he had lost his eyesight. Auktionshaus für Altertümer Glückselig in Vienna held the auction Wiener-Porzellan Sammlung Karl Mayer from 19 to 21 November 1928 in Vienna. The richly illustrated auction catalogue had 529 lots. Otto von Falke, who retired in 1927 as the director general of the Berlin museums, provided descriptions of those items absent from Folnesics's publication and also wrote the foreword. The collection was given a low valuation of 300,000 schillings but the interest by Austrian and international buyers was such that the proceeds ran to 824,000 schillings.
After the annexation of Austria to the Nazi German Reich in March 1938, Mayer, by now eighty-three years old and completely blind, was persecuted as a Jew and required to declare his assets to the Nazi authorities. His declaration of assets of 29 June 1938 listed only a few artworks. In February 1941 he was evicted from his apartment at Operngasse 6 and forced to move to a collective apartment at Ebendorferstraße 10/7 in the 1st district. He was admitted on 9 March 1942 to the Jewish Community hospital at Seegasse 9 in the 9th district, where he died ten days later. He was buried on 27 April 1942 in the Central Cemetery.