Spain's Aleix Espargaro won his first MotoGP race at the 200th attempt in Argentina on Sunday and tearfully admitted: "It's really special".
The 32-year-old also gave Aprilia a maiden triumph in the sport's premier class while he took over the lead of the world championship after three rounds.
Jorge Martin, on a Ducati-Pramac, and Suzuki's Alex Rins made it an all-Spanish podium.
"I am really happy, I have waited a very long time," said a tearful Esparago who joined Aprilia in 2017.
"It's particularly special as it was my 200th race in MotoGP."
In all, Espargaro has taken part in 283 grand prix across the sport's three classes since his 2004 debut in the now defunct 125cc class.
"Everything was in place, we were solid on the pace, but it was double pressure because everyone was telling me it was going to be easy, but it wasn't.
"The last laps were my strongest. I thank everyone at Aprilia, I think we really deserve it, and the other incredible thing is that we are leading the championship.
"Six years ago, nobody believed in Aprilia."
Espargaro started from pole, his first since his Suzuki days seven years ago at the Catalunya Grand Prix in Barcelona, but Martin immediately roared past.
The 24-year-old Martin, chasing his second MotoGP win after the 2021 Styrian Grand Prix, held off his compatriot for large parts of the 25-lap race.
Espargaro twice nipped past, only to run wide. However, it turned out to be third time lucky when he made another daring overtake finally stick on the 18th lap, holding the lead comfortably to the flag.
CRASH FOR 16-YEAR-OLD
Defending world champion Fabio Quartararo of France was only eighth on the factory Yamaha.
Another Spaniard, Joan Mir was fourth on a Suzuki ahead of Italy's Francesco Bagnaia, the championship runner-up in 2021, riding a Ducati.
Nine different riders have been on the podium at the opening three races of the season but it is Espargaro who leads the way with a seven-point advantage in the standings over South Africa's Brad Binder of KTM.
Former championship leader Enea Bastianini of Ducati-Gresini, who won the season opener in Qatar, is third overall, nine points off the pace.
The Argentina Grand Prix had been cancelled in 2020 and 2021 due to the pandemic.
Six-time MotoGP world champion Marc Marquez, who won the race in 2019, missed Sunday's event after suffering double vision following his high-speed crash last time out in Indonesia.
The fourth round of the championship takes place next weekend with the United States Grand Prix at Austin, Texas.
Celestino Vietti won the Moto2 race for his second victory this season having also triumphed in Qatar.
Vietti, who rides for Valentino Rossi's VR46 Racing Team, now has a 21-point lead in the standings.
The Hondas of Somkiat Chantra, the winner in Indonesia last time out, and Ai Ogura completed the podium.
Polesitter Fermin Aldeguer, bidding to become Moto2's youngest race winner at 16, crashed out after contact with Vietti.
It was desperate luck for Aldeguer after he had set a new lap record in the warm-up earlier Sunday.
In Moto3, Sergio Garcia, who had started on pole position, claimed victory despite being down in third place at the start of the final lap.
The Aspar team rider swept past Dennis Foggia and teammate Tatsuki Suzuki to claim his first win of the season and take the overall lead in the championship.
Ayumu Sasaki rounded out the podium despite having to complete a long lap penalty.
MotoGP RESULTS
1. Aleix Espargaro (ESP/Aprilia) 41min 36.198sec,
2. Jorge Martin (ESP/Ducati-Pramac) at 0.807sec,
3. Alex Rins (ESP/Suzuki) 1.330,
4. Joan Mir (ESP/Suzuki) 1.831,
5. Francesco Bagnaia (ITA/Ducati) 5.840,
6. Brad Binder (RSA/KTM) 6.192,
7. Maverick Vinales (ESP/Aprilia) 6.540,
8. Fabio Quartararo (FRA/Yamaha) 10.215,
9. Marco Bezzecchi (ITA/Ducati-VR46) 12.622,
10. Luca Marini (ITA/Ducati-VR46) 12.987
WORLD CHAMPIONSHIP STANDINGS
1. Aleix Espargaro (ESP/Aprilia) 45 pts,
2. Brad Binder (RSA/KTM) 38,
3. Enea Bastianini (ITA/Ducati-Gresini) 36,
4. Alex Rins (ESP/Suzuki) 36,
5. Fabio Quartararo (FRA/Yamaha) 35,
6. Joan Mir (ESP/Suzuki) 33,
7. Miguel Oliveira (POR/KTM) 28,
8. Johann Zarco (FRA/Ducati-Pramac) 24,
9. Jorge Martin (ESP/Ducati-Pramac) 20,
10. Pol Espargaro (ESP/Honda) 20