Goldberg was hired by the city of San Francisco as an engineer; however, his fondness for drawing cartoons prevailed, and after just a few months, he quit the city job for a job with the San Francisco Chronicle as a sports cartoonist. The following year, he took a job with the San Francisco Bulletin, where he remained until he moved to New York City in 1907.
He drew cartoons for five newspapers, including the New York Evening Journal and the New York Evening Mail. His work entered syndication in 1915, beginning his nationwide popularity. He was syndicated by the McNaught Syndicate from 1922 until 1934. A prolific artist, Goldberg produced several cartoon series simultaneously, including Mike and Ike (They Look Alike), Boob McNutt, Foolish Questions, Lala Palooza and The Weekly Meeting of the Tuesday Women's Club.