Beginning as touring bassist for Ministry's 1986 Twitch tour, Barker collaborated with frontman Al Jourgensen and collectively released The Land of Rape and Honey in 1988. Although many musicians briefly contributed to Ministry in the nearly two-decade period after Barker joined the band, he and Jourgensen were the only continuous members. The dynamics between these two different personalities came to shape Ministry's sound, along with a number of side-projects which they were involved in together.
In 2003, Barker left the band a year after the release of their eighth album Animositisomina. The decision was made officially after the death of his father. Despite being in Ministry for almost 18 years, Jourgensen did not do anything to spur his departure. "Over the years we've had strained relations as well as good times, and the last tour was no different than any other tour. That means it was extremely difficult and very intense and lots of fun," Barker had said.
It is often believed that Jourgensen and Barker were close bandmates and the latter played a huge creative role in the band. Jourgensen rebuffed these claims saying that their relationship was more like an arranged marriage and "acrimonious." He said that they were never friends but business partners. Since leaving Ministry, Barker has distanced himself from Jourgensen and the two almost have nothing good to say about their relationship in the band.
Barker was quoted in a 2011 interview that it was "tough to watch" the band's Fix: The Ministry Movie documentary as he could no longer associate himself with the band. When asked in a 2015 interview if he will ever work with Jourgensen again, he replied, "I'm fairly confident we will not work together. We have zero relationship now." When asked why he left Ministry, he said because he was no longer willing to put up with the stupidity and decided that it was enough.
Barker has since moved on to other things and in 2016, he seems to have made peace with Ministry more or less. "Of course, that was a very intense time and extremely rewarding. That was quite a while ago and I rarely think about it. I'm still fascinated with the heaviest, ugliest music and it's now hard to find the time for those pursuits. I am not in direct contact with Al these days."
In 2018, Jourgensen got back in touch with Barker. He contacted Barker while they both made appearances at screenings for the documentary Industrial Accident: The Story of Wax Trax! Records. Jourgensen has stated he is eager to collaborate with Barker very soon.
Since 2003, Barker has spent his time recording new material, producing such acts as I Love You But I've Chosen Darkness and collaborating with artists such as Stayte (on their 2007 Cognitive Dissonance (The Art of Lying To Yourself) EP). He joined U.S.S.A. with Duane Denison (Tomahawk, ex-The Jesus Lizard) as bassist. The first album from his solo project Flowering Blight, entitled The Perfect Pair, was released on November 19, 2008 via the official website.
In 2011, Barker remixed the Deadly Apples song Self Inflicted Oppression with samples from Ministry's Psalm 69. The remix was featured on the soundtrack for the documentary film Fix: The Ministry Movie.