Dana Snyder got the job of voicing Master Shake through an old college friend who went to high school with Dave Willis. Willis was looking for voice actors and asked his friend if she knew anyone with a weird voice, so she recommended Snyder. His first "audition" was leaving a drunken, abusive message on Dave Willis' voice mail at 3am. Willis loved it but accidentally erased it and asked Snyder to re-record it, which he did, but sober this time. Willis wasn't as keen on this one and asked him to do it like he did the first time. Snyder dutifully went out with some friends, got drunk, and left another 3am voice message. He was given the job.
After the episode "Super Hero" (where Shake exposes himself to toxic/radioactive waste in an attempt to gain super powers), every time Master Shake throws an object to the ground, it explodes. Some past examples include a phone, a remote control, the chair, a toilet brush, and a losing lottery ticket. Shake even refers to this phenomenon in one episode.
The show is created using Adobe Photoshop images, animated using Adobe After Effects and edited using Apple's Final Cut Pro. Writing the script takes Dave Willis and Matt Maiellaro around four or five weeks, after which they spend a week making a rough show on video and get the voiceover work done. The animators use the QuickTime video as a reference and spend another five weeks making the finished 11 minute episodes. The whole thing costs around $60,000 per episode (an uncommonly low figure for an animated TV series).
When the teens move around, they make sounds according to the food that they are. Meatwad, for instance, makes a squishy sound. The creators actually bought eight pounds of hamburger meat and squished it with rubber gloves to get that sound. They also bought a milkshake and got some sounds from that too.
The picture of Doctor Weird's castle in New Jersey is actually taken from an episode of The Real Adventures of Jonny Quest (1996) called "Escape to Questworld". It's a shot of The Belle Isle Institute, where Dr. Jeremiah Surd is housed. The shot was originally the Himalayan outpost from the "Monster in the Monastery" episode of the 1964 series.
Dave Willis and Matt Maiellaro created a pilot episode for a show called "Spacecataz", which featured two recurring villains from the Aqua Teens series: the Mooninites and the Plutonians. Though the show was never actually produced, the pilot episode was cut into several little parts and placed before Aqua Teen episodes during season four, taking the place of the "Dr. Weird" opening shorts for a while.
Through Seasons 1-3, when the show ended, the logo for Williams Street Studios was followed by the image of a skull and crossbones with the Cartoon Network logo as the skull's teeth. Over that would be the sound of Matt Maiellaro, the show's co-creator, shouting, "Skull!"