Jameson was still in High School when he began working as a part-time reporter for the Daily Bugle. Years of dedicated hard work opened many doors for the young man and he eventually became so successful he was able to purchase the Daily Bugle, becoming the editor at the same time. As the editor, he used his paper as a means of supporting civil rights of minority groups and to expose organized crime. However, when a young man named Peter Parker was bitten by a radioactive spider and became the amazing Spider-Man, Jameson began a personal crusade to exterminate the web-slinger.

Jameson's first attempt was when he paid Dr. Farley Stillwell, a well-known researcher in animal mutations, to create a super-villain that could destroy Spider-Man; thus the Scorpion was born. However, Jameson's plan was quickly ruined when Spider-Man defeated the Scorpion. Ever since his creation, the Scorpion had blamed Jameson for his condition, and has since then, tried several times to kill him. However, Spider-Man has always been around to stop him.

Months later, Jameson hired Dr. Spencer Smythe, the mastermind behind the creation of the infamous "Spider-Slayers", to use one of his robots to capture Spider-Man in order to reveal his identity to the entire world. Smythe's first robot failed to defeat Spider-Man to Jameson's discontent, so the latter decided to stop funding Smythe's experiment. Smythe then became obsessed with building bigger, stronger, and more dangerous robots – his hatred for Jameson growing at the same time. All of his foolish attempts to defeat Spider-Man and Jameson came to an end when he died from overexposure to radioactive materials used in creating his Spider-Slayers.

His years at the helm of the Daily Bugle came to and end when he lost control of the Daily Bugle to Thomas Fireheart (a.k.a. The Puma), who purchased 51% of the company stock. Fireheart, as Puma, felt he owed a debt to Peter Parker, who he knew was Spider-Man, after the latter had fought by his side against the Beyonder in the "Secret Wars II" limited series. Fireheart offered the position of publisher to Joe Robertson and made sure that the Bugle would only print positive stories about Spider-Man from that moment on. Fireheart ran the Bugle for quite a while until he eventually sold it back to Jameson for a measly dollar.