Before his comic book career began, DeCastro created artwork for the band Mucky Pup, with whom he was friends. He provided the interior art for their 1987 album Can’t You Take a Joke?, and the cover art for their 1989 album, A Boy In A Man’s World.
Nelson broke into the American comic book industry in 1992 doing airbrushed cover work for Dark Horse Comics series, such as Insider Vol. 2 #6 and the four-issue miniseries RoboCop: Prime Suspect. In 1993 he wrote and illustrated his own creator-owned horror character, Eudaemon, in the anthology Dark Horse Presents #72-74, for which he provided the first issue’s cover. He would later publish through Dark Horse a three-issue Eudaemon series, which he wrote, pencilled, and inked, and for which he provided airbrush-painted covers.
His first comic work for the Big Two publishers was a 6-page comic book story he penciled and inked for Marvel Comics’s Custom Comic division. He would also provide the publisher with a painted cover for Marvel Comics’ Ghost Rider #18 in 1993. His first work for DC Comics doing interior illustration for Team Superman Secret Files and Origins #1, which was published in 1998. Other DC work during the 1990s includes Birds of Prey: The Ravens #1.
In 1999, Nelson worked for Marvel Comics, beginning with a painted cover and the interior art for X-Men: The Magneto War #1. His other Marvel work that year included issues of Generation X, Black Panther and X-Force.
Nelson continued to work for Marvel Comics in the early 2000s, on such titles as Iron Man, Ant-Man’s Big Christmas, Generation X, Marvel Knights, Elektra, and Inhumans.
He also provided work for DC Comics, on Birds of Prey and 2004’s The DC Comics Encyclopedia. His other mid-2000s work for DC included doing inks for Superman: The Journey and inking over John Byrne’s pencils and providing his first interior color work on Action Comics #831.
Nelson branched out into educational comics with 2005’s The Home Depot: Safety Heroes, a giveaway from the Home Depot featuring several Marvel Comics characters, as well as into Marvel’s mature readers imprint, MAX, with Doctor Spectrum, two issues of which he inked, and Marvel’s Ultimate line, providing interior inks for three issues of the miniseries Ultimate Nightmare and Ultimate Galactus Trilogy.
Although he mostly worked for Marvel Comics in the late 2000s, in 2008 Nelson provided the interior pencils and inks for DC’s Green Lantern Corps #21-22.
2009 marked Nelson’s first foray into writing for The Big Two publishers, with the story “The Strange Bonds of Strange People”, which appeared in Astonishing Tales: The Thing #1 by Marvel Digital Comics. He also provided inks for War of Kings: Savage World of Skaar, for which he was credited on the cover as “DeCastro”, and not “Nelson”, as he is typically credited. That year he also inked issues of Incredible Hercules, and penciled and inked Iron Man: Iron Protocols.
As of 2010, Nelson teaches a Drawing for Cartoonists course at Manhattan’s School of Visual Arts, where he himself once studied.
DeCastro has illustrated cards for the Magic: The Gathering collectible card game.