Making his first appearance in 2016, Johnson (17-10) dropped Poirier with the combination of a counter right hook and straight left hand in the main event of UFC Fight Night in Hidalgo, Texas. He immediately followed Poirier (20-5) to the canvas and unloaded a series of unanswered punches to bring in referee Dan Miragliotta to wave it off.
The loss is Poirier's first since moving up from the featherweight division in 2015. It is the eighth career knockout for Johnson, who underwent shoulder surgery earlier this year.
"I'm just coming in here to show people I'm serious about this division," Johnson said. "Conor McGregor and Nate Diaz getting paid all that money and they're out there scrapping, having a sparring match. Pay me baby, what's up?
"I say it over and over again: I have the fastest hands in this division. I'm the most dangerous guy in this division. I'm ready to test anyone. Give me anybody."
Fighting out of Blackzilians in Boca Raton, Florida, Johnson snapped a two-fight skid. He suffered a highly controversial split-decision loss to Beneil Dariush in April 2015 and then another decision loss to Diaz in December. Diaz used that victory to catapult himself into a big money fight against McGregor in 2016.
Before Saturday, Johnson told ESPN.com he was "happy" for fighters like McGregor and Diaz, who have recently netted disclosed fight purses in the millions. Johnson, 30, has been fighting in the UFC since 2010, with an overall record of 9-5.
After initially walking away from Poirier following the knockout, Johnson went back toward his fallen opponent and stood over him momentarily with arms raised. He then yelled something in Poirier's direction. The two eventually did embrace after the result was read.
After taking apparently no damage in the fight, Johnson called for a spot on the Nov. 12 UFC 205 pay-per-view event at Madison Square Garden in New York.
"I want on that New York card," Johnson said. "Anybody, let's go."
Brunson knocks out Hall
Middleweight Derek Brunson (16-3) extended his winning streak to five with a TKO finish over Uriah Hall (12-7) at 1:41 of the opening round. After an early clinch, Brunson dropped Hall with a straight left and followed him to the ground with punches. Hall fell violently to the floor but did appear to be blocking Brunson's follow-up shots. Referee Herb Dean opted to step in and Hall immediately jumped up to protest the stoppage.
Fighting out of Jackson-Wink MMA, Brunson now has 12 career finishes. He is 7-1 in the UFC, with his only loss coming to Yoel Romero via TKO in January 2014. Hall, 32, falls to 5-5 in the UFC.
Skelly scores submission in 19 seconds
Featherweight Chas Skelly (16-2) wasted no time hanging a finish on Maximo Blanco (12-8-1), as he locked in a D'Arce choke just 19 seconds into the first round. It is the fastest finish in UFC featherweight history.
Skelly, who trained for this fight out of Blackzilians in Boca Raton, Florida, sprinted across the cage at the opening bell and landed a flying front kick that pushed Blanco to the floor. In the ensuing scramble, Skelly rolled into the choke and put Blanco out cold.
It is the ninth submission win of Skelly's career and improves him to 5-1 in his past six fights.