Stir together salt, pepper, smoked paprika, chili powder, cumin, onion powder, and cayenne. Rub all over the brisket.
Heat the oil in a large skillet over medium-high. Sear brisket 3–4 minutes per side until deeply browned.
Spread the sliced onions and minced garlic in an even layer in the slow cooker.
Whisk together barbecue sauce, beef broth, brown sugar, mustard, Worcestershire, vinegar, and liquid smoke.
Set the brisket on top of the onions. Pour the sauce mixture over and around the meat.
Cover and cook on Low for 8–10 hours, until the brisket is fork-tender.
Lift brisket to a board and tent with foil for 15 minutes to rest.
Skim fat from the cooking liquid. Simmer the sauce in a saucepan 8–10 minutes to thicken, if desired.
Slice against the grain or shred. Toss with some sauce and serve the rest alongside.