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In a small bowl, mix together the chili powder, garlic powder, salt and pepper.
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Pat the brisket dry with a paper towel. Sprinkle the spice mixture on both sides of the brisket.
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Place the brisket in a large soup pot and top with salsa, chilis, honey, and water. Mix just a bit and lift up the brisket to allow liquid to flow underneath it.
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Place the pot on the stove over high heat and bring to a boil. Turn the heat down to medium-low and simmer, covered, for 3 1⁄2 hours until fork tender. Uncover and cook for another 30 minutes, which will allow the liquid to thicken a bit. Turn off the heat.
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Carefully remove the brisket from the liquid and transfer to a heatproof bowl or cutting board. Let it sit to cool for 30 minutes or up to 1 hour.
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Use two forks to shred the brisket and transfer back to the pot of sauce. Mix and set aside.