He was recruited as the number 11 draft pick in the 1999 AFL Draft from Perth and made his debut for the Eagles in Round 4, 2000 against Adelaide.

Glass, who had a relatively low profile in a team of well known stars such as Ben Cousins, Chris Judd, and Daniel Kerr, was named as the All-Australian full-back in 2006.

On 9 November 2007, Glass was announced as the new captain of West Coast with the departure of Chris Judd to Victoria. Glass was appointed to lead the recovery of the club after a series of off-field scandals. West Coast had a poor year in his first year of captaincy, suffering from the loss of Judd and Cousins as well as from injuries to key players, including Glass himself.

Glass married Alicia Severin in December 2007. They have two daughters and one son. Glass has a commerce degree in finance and marketing from Curtin University. He completed a Master of Business Administration degree at the University of Western Australia in 2015 has previously worked as a consultant for Boston Consulting Group.

After a successful season playing all 22 matches in 2009, Glass won his second Club Champion award ahead of fellow defender Shannon Hurn. He followed this up two years later in 2011 where he won his third Club Champion award and third All-Australian selection. In 2012 Glass was given his fourth All-Australian selection and named as the captain of the All-Australian team.

On 12 June 2014, Glass announced his retirement due to injury, effective immediately.

At the end of the 2017 AFL season Glass accepted an assistant coaching position at Hawthorn. At the conclusion of the 2019 AFL Season, Glass returned to the West Coast Eagles as the List Manager after Brady Rawlings returned to the North Melbourne Football Club. In October 2019 Darren accepted a position back at West Coast as a player list manager, heavily involved in the recruiting process. Newly appointed captain Luke Shuey has welcomed his return.