Souza (25-5) finished the always dangerous Brunson via TKO at 3:50 of the opening round. The 185-pound contest headlined UFC Fight Night at Charlotte's Spectrum Center.
Before the bout, Souza, 38, admitted he contemplated retirement in 2017, after a pair of surgeries sidelined him during the second half of the year. The Brazilian willed himself to return, however, and was rewarded with Saturday's result.
"I feel great. It was hard to come back into training again," Souza said. "Two surgeries -- four months ago, I was in the hospital."
The finish came after Souza hurt Brunson (18-6) with a right head kick. Brunson went skating toward the fence, where Souza swarmed him with punches to the side of the head.
It's the second time Souza has gotten the better of Brunson, who fights out of nearby Wilmington, North Carolina. The two met under the Strikeforce banner in 2012; Souza won that bout via KO just 41 seconds in.
Brunson came out cautious in the first, showing Souza respect. He blitzed Souza with punches a couple of times during the round, but was backed off quickly by Souza's counter right hand.
Souza continued to hunt that right hand, but it was the right head kick that changed the fight.
For Souza, it's his first victory since a first-round submission against Tim Boetsch nearly one year ago. A UFC title shot has somehow eluded Souza to this point, despite an 8-2 record in the Octagon.
An interim middleweight title fight between Luke Rockhold and Yoel Romero is scheduled to headline UFC 221 on Feb. 10 in Perth, Australia. The winner of that bout is expected to face undisputed champion Robert Whittaker at a later date.
Fili takes close decision over Bermudez
Two judges scored the bout for Fili 29-28, whereas a third had it 30-27 for Bermudez. ESPN scored it 29-28 for Bermudez.
A member of Sacramento's Team Alpha Male, Fili scored a handful of surprise takedowns, but Bermudez quickly popped to his feet after each one. Fili scored with the jab and counter right hand, but Bermudez's pressure appeared to get the better of him as the fight progressed.
Bermudez, of New York, bloodied Fili's nose with jabs and roughed him up with flurries along the fence. He also had great success with the low leg kick, which affected Fili's mobility in the third round.
It's a tough result for Bermudez, who has dropped three in a row. Fili improves to 3-1 in his past four.
Gillespie makes quick work of local favorite Rinaldi
Referee Donnie Jessup stopped the bout at the 4:46 mark after Gillespie took Rinaldi's back and landed unanswered punches. It was essentially a grappling clinic by Gillespie, a former NCAA Division I national champion wrestler, as he easily took Rinaldi (13-5) down and advanced position.
Gillespie, of New York, moved from side control to mount and eventually to the back. It is the ninth finish of his career, and he is 4-0 in the UFC.
Rinaldi is 1-2 in the UFC. His only win came in the first round against Alvaro Herrera last August.
Dober outlasts Camacho in war of attrition
Camacho, of Northern Mariana Islands, executed several nifty trips in the first and third rounds, but he failed to do a ton of damage from top position. He also appeared to tire out midway through the second, which opened the door for Dober to dictate things on the feet.
Dober, 29, of Nebraska, landed several combinations to the body. He bloodied Camacho's nose in the second round and beat him to the punch in back-and-forth exchanges late.
It is Dober's fourth win in five fights. He said he expects going back to lightweight for his next bout, where the majority of his career has taken place. Camacho falls to 1-2 in the UFC.