In 1982, as a high school student at Mt. Lebanon High School, Skrenta wrote the Elk Cloner virus that infected Apple II machines. It is widely believed to be one of the first large-scale self-spreading personal computer viruses ever created.
Skrenta graduated from Northwestern University. Between 1989 and 1991 he worked at Commodore Business Machines with Amiga Unix. Between 1991 and 1995 he worked at Unix System Labs and from 1996 to 1998 with IP-level encryption at Sun Microsystems. He later left Sun and became one of the founders of DMOZ. He stayed on board after the Netscape acquisition, and continued to work on the directory as well as Netscape Search, AOL Music and AOL Shopping.
After his stint at AOL he went on to cofound Topix LLC, a Web 2.0 company in the news aggregation & forums market. In 2005, he and his fellow cofounders sold a 75% share of Topix to a newspaper consortium made up of Tribune, Gannett, and Knight Ridder. In the late 2000s he headed the startup company Blekko Inc, which was an internet search engine. Blekko received early investment support from Marc Andreessen and began public beta testing on November 1, 2010. In 2015 both the company and search engine were acquired by IBM for their Watson computer system.
He was involved in the development of VMS Monster an old MUD for VMS. VMS Monster was part of the inspiration for TinyMUD. He is also known for his role in developing TASS, an ancestor of tin, the popular threaded Usenet newsreader for Unix systems. In 1989 he started working on a multiplayer simulation game. In 1994 it was launched under the name Olympia as a pay-for-play PBEM game by Shadow Island Games.