Alex Rins won Sunday's Grand Prix of the Americas following a blunder from Ducati's MotoGP world champion Francesco Bagnaia.
Rins capitalised on a fall from leader and pole-sitter Bagnaia to claim the third leg of the season and end Honda's long winless run.
Luca Marini (Ducati-VR46) took second with Fabio Quartararo (Yamaha) in third.
Bagnaia won Saturday's sprint but left the showpiece race in Austin pointless as Marco Bezzecchi, who finished sixth, extended his lead at the top of the riders' standings.
Rins, a winner for Suzuki at the circuit in 2019, was gifted the lead before the halfway stage of the 20-lap race when Bagnaia's bike hit the Texan tarmac.
Second to Bagnaia in the sprint 24 hours earlier, Rins controlled the race perfectly from that moment on for his sixth win in motorcycling's premier class and his first for his new team.
"I was trying to push 'Pecco' (Bagnaia), in the chicanes pushing so much, so I'm very happy, and so proud of the team," said Rins, beaming from beneath a traditional Texan cowboy hat.
Marini crossed the line almost three and a half seconds back for his best result in MotoGP.
"I was careful at the beginning, I didn't want to make a mistake," he said,
"I had good pace. After Pecco's crash I tried to overtake Fabio and catch Alex, but he was so strong and Honda had the best bike, they were impossible to beat but I'm really satisfied with my result."
Bezzecchi, who won the main event in Argentina, takes an 11-point lead over Bagnaia to the fourth race of the season in Spain at the end of the month.
Rins, 27, moves up to third, six points behind Bagnaia, for whom this blunder followed the one he made when nailed on for second in Argentina.
"I don't understand, I'm so disappointed and quite nervous as it wasn't my fault," said a dejected Bagnaia, who was within one point of Bezzecchi in the rider's standings going into the race.
Bagnaia was far from the only faller, with Alex Marquez, Jorge Martin and Aleix Espargaro crashing in the opening lap as only 13 of the 22-strong grid completed the race.
Rins' success was a boost for Honda, with their last win in the premier class dating back to Marc Marquez's win on the factory bike in the Emilia Romagna Grand Prix in October 2021.
Marquez, a seven-time winner on the Austin circuit, and last year's Grand Prix of the Americas winner Enea Bastianini, were both missing from Sunday's race as they recover from injuries sustained in the season-opener in Portugal.
The Moto2 race went to Spanish teenager Pedro Acosta, his second win of the campaign after a tight battle with Italian Tony Arbolino, who maintained his lead in the riders standings.
Another Spanish teenager Ivan Ortola took the Moto3 honours for his first career win as fifth-placed Daniel Holgado remained at the head of the championship on 49 points with Diogo Moreira.
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