Caston was born and spent most of his early life in Baton Rouge, Louisiana. He attended Louisiana State University and majored in Computer Science. After finishing school he moved to Dallas, Texas. While in Dallas he began work on what would become Megatokyo.

His son's middle name (Case) was said to have been chosen because of Rodney's appreciation of the novelist William Gibson. In Gibson's cyberpunk book Neuromancer, the main character was named Henry Dorsett Case.

Caston is the co-creator and writer of the comic MegaTokyo. MegaTokyo was one of the largest and most successful early webcomics to transition from online to print, the success of it and other early properties such as Penny Arcade and PvP went on to influence an entire generation of webcomic creators. He has since parted ways with his partner, Fred Gallagher and relinquished control of Megatokyo. He is credited for the first two published volumes of Megatokyo. His alter ego, Largo, was the insane gaming fanatic while Fred Gallagher's alter ego, Piro, played the straight man. Caston quietly parted with Gallagher from Megatokyo. The legal details of the split are private and not much was said about it at the time.

Caston's connections to software designers and writers at Bioware landed his alter ego cameos in two of their games. In Shadows of Amn there is a NPC tavern keeper named Largo; and in Star Wars Knights of the Old Republic there is an NPC named Largo that you can either help, not help, or kill for fun on the first planet. About - RCaston.com | RCaston.com

In early 2005, a controversy erupted after Scott Kurtz of PvP wrote a forum post that congratulated Caston on his impending fatherhood as well as accusing Fred Gallagher of stealing Megatokyo away from Caston. Due to the fan speculation that ensued, Gallagher was forced to explain the reason for the split, citing creative differences and insisting that the breakup was amicable. Caston then gave his version of the events. The truth about Megatokyo? | RCaston.com

While speaking at a panel at A-Kon 15, Caston responded directly to the reason for the split, saying: "We had creative differences, I was creative, he was different." However he maintains that the two are still friends.

Caston has been a guest speaker at various conventions such as Otakon, A-Kon, Animefest, Ohayocon and others.

Megatokyo comics are currently published by D.C. Comics, and have been published by Dark Horse Comics, and Studio Ironcat. As of August 8, 2010, six volumes are available for purchase. After Volume Two, Rodney Caston's name no longer appears on the publication.

• Megatokyo Volume 1: Chapter Zero (Megatokyo vol.1 1st ed.) ISBN 1-929090-30-7
• Megatokyo Volume 1, 2nd ed. ISBN 1-59307-163-9 (published March 21, 2004)
• Megatokyo Volume 2 ISBN 1-59307-118-3 (published January 22, 2004)
• Megatokyo Volume 3 ISBN 1-59307-305-4 (published February 2, 2005)
• Megatokyo Volume 4 ISBN 1-4012-1126-7 (published June 21, 2006)
• Megatokyo Volume 5 ISBN 1-4012-1127-5 (published May 25, 2007)
• Megatokyo Volume 6 ISBN 1-4012-2481-4 (published July 14, 2010)

In July 2004, Megatokyo was the tenth best-selling manga property in the U.S. [1]. Volume3's highest ranking in bookscan is 3 ending February 20, 2005.[2] Which broke all previous records for sales of an American manga until that time.

Caston is a civil libertarian and active member of the Libertarian Party. In 2008, he ran, unsuccessfully, for Collin County Constable, in the state of Texas against Republican Chuck Presley, Sr. He received 19079 votes (19.44% of the total votes cast) to Presley's 79039 votes (80.56% of the total cast).