A Disney scout recruited him about 1934, and he decided to accept the job since it paid $10 per month more than the department store did. Noble was put to work on backgrounds for the Silly Symphonies cartoon series. At that time the Disney backgrounds were required to be done in transparent watercolor wash, which was technically difficult because correcting a mistake was usually impossible, requiring a full new attempt.
Snow White and the Seven Dwarfs was the first feature length film Noble worked on. This was followed by background work on other Disney features, notably the Rite of Spring sequence in Fantasia. Noble also did story development for the Dance of the Hours in that film. For Dumbo, he did color coordination and character design, including work on the pink elephant sequence.
Noble joined the Disney animators' strike in 1941; it lasted five weeks and became bitter. When he returned after the strike was settled, his office was moved to an ex-broomcloset and he was left without assignments. Soon he was laid off and his career at Disney was at an end.
The outbreak of World War II lead Noble to enlist in the Army Signal Corps. He was eventually assigned to a small unit headed by Ted Geisel (later to become well known as Dr. Seuss). The unit was based at the Fox studios and under Col. Frank Capra. It worked on posters and booklets, and on a cartoon series called Private Snafu. The unit did the writing, storyboards, and background designs; the cartoon production was contracted out. Warner Bros. won the contract for Private Snafu, and the WB animation director Chuck Jones worked on the series. Following the war Noble did freelance work in the industry and then took a position doing art for a filmstrip production company in St. Louis.
At Warner Bros., Noble worked with Jones for a decade, over which time the team did over 60 cartoons. Turning away from the fussy realism of Disney backgrounds, Noble grew into styles using shape and color to define the space. The graphic look of his backgrounds could vary widely from film to film; he tried to make the backdrop fit the mood of the film. Noble says:

A break of about a year came during this period, when Noble spent time working at Famous Studios in the wake of Warner Bros. shutting down their cartoon unit, and did not return immediately upon the studio re-opening. In this period, Jones had his layouts done first by former Disney artist Ernie Nordli, who used an even more abstract (albeit less consistent) style than Noble, and then later by Noble's predecessor, Robert Gribbroek, who largely discarded the styles used by Noble and Nordli, and reverted to the look of Jones' earlier cartoons. Eventually, Jones coaxed Noble into returning to Warner Bros., and the two men would work together for the next few decades.
In the early 1960s, Noble started receiving co-director credit on a number of the Jones-unit productions. This reflected his increased involvement in many phases of the creation process beyond just the layouts, pulling things together and ironing out rough spots.
The bread-and-butter work for the first couple of years was producing cartoons starring MGM's Tom & Jerry characters, but there were an assortment of other projects. One was The Incredible Mr. Limpet (1964), a combined live action & animation feature. Noble co-directed The Dot and the Line (1965) which won the Oscar for short subject (cartoon). He also designed the 1969 feature The Phantom Tollbooth.
Noble started working again with Ted Geisel for the first time since the war, doing the design for the TV feature How the Grinch Stole Christmas! (1966). He later did design and layout work on a number of other Dr. Seuss features, first at MGM (Horton Hears a Who! (1970)), and then at the DePatie-Freleng studios (e.g. The Cat in the Hat (1971), The Lorax (1972), Dr. Seuss on the Loose (1973)).
About 1989 Noble did development work on Steven Spielberg's Tiny Toon Adventures, and did writing and design for the "Duck Dodgers Jr." episode.
In the mid-1990s Noble rejoined Jones at Chuck Jones Film Productions, serving as art director on Chariots of Fur (1994) and color consultant on several other productions, including Pullet Surprise.
While at the Jones studio, Noble began supervising, training, and mentoring young artists just out of (or still in) school. These artists came to be known as the 'Noble boys and girls'. Many of them became involved in "Noble Tales," a planned series of animated shorts based on folk tales. One such film was Al Tudi Tuhak (1999).
Noble continued to be active in a variety of animation projects, including consultation with Disney artists for their first watercolor backgrounds in half a century (for Lilo and Stitch). Noble died in 2001 at his home in La Crescenta, California.