The Motion Picture Screen Cartoonists Guild, then known as the Hollywood Screen Cartoonists, held their first union meeting in 1937. A formal constitution was drafted in 1939, and the name Screen Cartoonists Guild (SCG) was adopted. In 1940, William Littlejohn became the Guild's president. After their first year as a union, the SCG represented cartoonists at Metro-Goldwyn-Mayer (MGM) and the Walter Lantz Studios. The Guild then consisted of approximately 115 members. Through successful collective bargaining, the SCG was able to significantly raise the average wage paid to the industry's animators.

Walt Disney Studios, with its 700 potential members, soon became the SCG's major organizing target. Disney employees belonged to the Federation of Screen Cartoonists (FSC), an organization which the SCG identified as a "company union." The FSC and the Disney Studios' management vehemently denied these allegations by the SCG. The Guild's successful organizing drive of Disney cartoonists quickly lead to the 1940/1941 Disney strike. The strike resulted in a bitter defeat for Disney and the Federation, while becoming a decisive victory for the SCG.

The SCG cast their lot with the Painters Union (International Brotherhood of Painters, Decorators and Paperhangers of America), an affiliate of the American Federation of Labor (A.F. of L.), but had to fight a jurisdictional battle with the International Alliance of Theatrical and Stage Employees (I.A.T.S.E.) for union recognition. The Hollywood Cartoonists then became Local 852 of the Painters Union.

Having successfully organized the Hollywood industry, the SCG soon tackled the New York animation industry. In 1944, the SCG sent its organizers to New York City to form Screen Cartoonists, Local 1461. This move also proved to be a successful venture, although in 1951, Local 1461 became involved in a tough jurisdictional dispute with the I.A.T.S.E., which was then led by Roy Brewer.

In 1947, the Motion Picture Screen Cartoonists Guild would face one of its first major defeats. Cartoonists in New Rochelle were asking for salaries comparable to those paid by other major studios. Not receiving satisfaction, the SCG organized a strike at Terrytoons, Inc. The cartoonists lost their fight in the strike, which lasted over twenty-eight weeks. Striking animators received support funding from other unions, but Terrytoons, Inc. was able to continue operating by hiring New Rochelle high school students to work during the strike.

In 1952 the Screen Cartoonists Guild changed its name to the Motion Picture Screen Cartoonists, and in 2002 changed to The Animation Guild.