Van Sciver was born in Utah and grew up in southern New Jersey. He decided on a career in the comic book field after seeing Superman: The Movie as a child, but read comics "mostly just... for the pictures, until John Byrne's The Man of Steel in 1986, when he began reading them more intently.
Van Sciver was involved in art in various forms before his comics work, speaking in 2005, he said:
All through high school I did all kinds of strange art jobs for money. I painted murals of Native Americans. I took a much envied job at the Cherry Hill Mall as a caricaturist. I had to wear a tuxedo, but I was 'Goth', so I also wore eye-makeup and a big clunky ankh around my neck, just under my bowtie. Because of that job, I did private parties where I'd basically show up at your Bar Mitzvah like a clown and draw all of your friends. That somehow led to a job where I illustrated about 12 children's books, which somehow led to a job where I designed bootleg Beavis and Butt-head neckties for some criminal Pakistani business, which led straight back to me doing airbrushed t-shirts that said 'Insane in the Membrane'.
Van Sciver cites Chris Claremont and Jon Bogdanove's Fantastic Four vs. the X-Men as a strong influence, telling a group of fans at Comic-Con International, "I'm trying in my own comics to recreate the feeling I got from that four-issue miniseries."
Van Sciver entered the comics industry at age 19 with what he called "a horrible little character called Cyberfrog", written and drawn by him and published by Hall of Heroes and, later, Harris Comics. He has contributed to a number of series for Marvel Comics and, primarily, DC Comics. Titles include his own Cyberfrog and such titles as New X-Men, The Flash: Rebirth, Green Lantern, and Superman/Batman.
Van Sciver's first major work for DC Comics was on the series Impulse, with writer Todd Dezago. Van Sciver recalled that Paul Kupperberg offered him a fill-in role on the series, with the chance to try to save the title.
Many of Van Sciver's most notable works have been produced in collaboration with writer Geoff Johns. Van Sciver feels he may have had a "bad influence" on the writer, working with him early on the superhero-horror one-shot The Flash: Iron Heights. The artist described his approach on the issue as "taking well-known, maybe well-worn superhero concepts, make them scary, make them upsetting in some way."
For Marvel Comics, Van Sciver produced several issues of Grant Morrison's New X-Men, starting as a two-issues-per-year fill-in artist for regular series artist Frank Quitely. Initially intending to also work on an X-Men miniseries with Johns while producing his small yearly commitment to Morrison's story, Van Sciver soon found himself asked to produce more and more issues, until a third 'regular' artist (Igor Kordey) was brought on board, and the Johns-penned miniseries was abandoned. Van Sciver is fond of inserting hidden elements in some of his work, including the incorporation of the word "sex" onto almost every page of New X-Men #118. In issue #133, Von Sciver helped create the character Dust, which Strömberg praised in a comics encyclopedia as a respectful, though somewhat Americanized, portrayal of a Muslim in comics.
In 2004, Johns and Van Sciver brought Hal Jordan back to the DC Universe as Earth's main Green Lantern officer in the six-issue miniseries Green Lantern: Rebirth, before the duo re-launched the Green Lantern title itself with a new volume. Van Sciver's work on the Green Lantern mythos explained and retconned many elements of the character's backstory which some fans and writers found nonsensical, such as the reasons of the power rings uselessness against the color yellow, and Hal Jordan's transformation into the supervillain Parallax.
In 2007, Johns, Van Sciver, Dave Gibbons and Ivan Reis produced the eleven-issue "Sinestro Corps War" across the two Green Lantern monthly titles, the second part of a trilogy of Green Lantern tales. This story launched the Sinestro Corps, the antithesis of the Green Lantern Corps, led by rogue Green Lantern Sinestro and his Qwardian yellow power ring. The series set the stage for a complete overhaul of the Lantern Corps, and introduced the emotional spectrum of power, which provides energy to seven different color variations of power rings.
In 2008, Van Sciver was the guest artist on an issue of Justice League of America vol. 2, #20 (June 2008). Van Sciver's 2009 work includes the six-issue mini-series The Flash: Rebirth, and variant covers for the Green Lantern and DC Comics company crossover storyline Blackest Night. Since 2016, as part of the DC Rebirth relaunch of DC's titles, Van Sciver has drawn several issues of the Hal Jordan and the Green Lantern Corps series.
In 2006, he penciled the cover art for Winger's fourth studio album. The cover art was sold as a poster called Guardian of Freedom.
In November 2012 Van Sciver became a host of the Fanboy Buzz comic book podcast, starting with episode #142.
As of August 2005, Van Sciver resided in Orlando, Florida.January 2010 Inkwell Awards Ambassador (January 2010 – present)