As a starving, homeless child living on the streets of Lakat, Madred scavenged for and ate raw taspar eggs, straight from the shell. He later recalled being beaten and having his arm broken by an older boy who stole the eggs, an experience from which he clearly never recovered. As an adult, he came to endorse the Cardassian military establishment, believing that it had the power to eradicate the poverty and violence that plagued Cardassia during his childhood.
During intensifying hostility between the Cardassian Union and the United Federation of Planets over territorial concessions, Madred captured Captain Jean-Luc Picard of the starship USS Enterprise-D by fabricating evidence of a metagenic weapon on the Cardassian planet Celtris III. There, Madred sought to uncover Starfleet's defense operations for Minos Korva by first drugging, then torturing Picard. Proving himself to be both cunning and brutal, Madred employed unique tactics which he felt stripped his victim of his individuality, stripping Picard of his clothing and referring to him simply as "Human". At the height of his sadism, Madred repeatedly showed Picard four bright lights, telling him that there were in fact five lights. When the captain refused to submit, he was tortured: a small device implanted in the captain's chest allowed Madred to inflict pain in any part of the body.
Ultimately, the Cardassians' intentions were exposed and Picard's release was ordered. Despite his best efforts, Madred was not able to successfully break Picard's will – although the captain later admitted that he came perilously close to breaking. (TNG: "Chain of Command, Part I", "Chain of Command, Part II")
Warner took over the role of Madred on three days' notice and, though he had previously appeared in Star Trek V: The Final Frontier and Star Trek VI: The Undiscovered Country, he knew nothing about the Cardassians from The Next Generation, as he recalled in a 2011 interview; "I took over on three days' notice. It was another makeup job. It was with Pat Stewart, who's an old colleague. It was great to be a part of that. I thought, 'Oh, I've done two of the others, the old classic ones, and here I am in The Next Generation. I'll go for it.' So I wasn't aware of it, of the Cardassians. I didn't know their history at all, except of course, that they weren't very nice." Due to the limited duration in which he had to prepare for the role, Warner did not have enough of time to memorize his lines. As such, they were written down on cue cards. He commented, "There was too much technobabble and dialogue that doesn't come naturally to me. So they wrote everything up for me. I don't mind people knowing this. Every line I said, I actually was reading it over Patrick's shoulder or they put it down there for me to do it." 
According to the script for "Chain of Command, Part I", the pronunciation for Madred was "muh-DRED".
Madred has appeared in several DS9 novels, including Andrew Robinson's A Stitch in Time (post Dominion War) and Ship of the Line by Diane Carey. In Robert Simpson's Lesser Evil, Madred appeared in scenes set in 2347 on Kora II, where he was a Glinn. Madred also appeared in the TNG short story "Four Lights" by Keith R.A. DeCandido in the anthology The Sky's the Limit, in which Picard and Madred are reunited during the Dominion War, with Madred in the Enterprise brig. Madred and Picard met again in the novel Ship of the Line, when Picard was sent into Cardassian space to free captured Starfleet officers, with Picard revealing that they were aided in their efforts by Madred's own daughter, who had become disgusted with her father's work after seeing him torture Picard.
During the comic miniseries Star Trek: The Next Generation - Perchance to Dream, when Picard was forced to enter his own mind to defeat a telepathic virus called the Chova with the aid of his other personalities (Sarek, Locutus, and Kamin), he used the mental image of the four lights Madred confronted him with to remind him of past victories while in his mind. Using the strength from this image, he was able to overcome Locutus when the latter attempted to gain control of his body, coldly informing Locutus that he would not give in before he was awakened.
In the original Cardassian Struggle arc for Star Trek Online, Madred had become the leader of the True Way organization and formed an alliance with a faction of Alpha Jem'Hadar to protect the True Way's mining operations. The player eventually captured him at Empok Nor. Madred was removed from the game when the Cardassian Struggle arc was revamped in early 2015.