A pile-up on the opening lap involving Franco Morbidelli, Alex Marquez, Marco Bezzecchi and Augusto Fernandez had resulted in a red flag, but all four were unhurt and able to take their place on the grid again for the 11-lap encounter.
Binder and team-mate Jack Miller fought it out at the front on the factory RC16 machines in a breathless race, but it was the South African who gained the upper hand in the closing stages.
After an unsuccessful attempt to make a decisive pass, with Binder running slightly wide on the brakes, he made his move stick on the penultimate lap.
He extended his lead to hold a valuable advantage going into the final lap and went on to win by four-tenths from 2022 world champion Francesco Bagnaia (Lenovo Ducati), who inherited second from Miller after the Australian ran wide on the last lap, missing the chance of a KTM one-two on the rostrum.
Binder, celebrating KTM's first premier class victory at Jerez, said: “Today was a tough one. With the red flag at the beginning I made sure I got a better start the second time around, and went straight to the front.
“I just had to take it a bit easy to try and bring the tyres up.
“I tried to stay comfortable and super-close to Jack because he had a great pace, and to be able to fight to the end, push, and come home with the win is incredible,” he added.
“I need to say a massive thank you to my team, fantastic to have both of us up on the podium, they've been working so terribly hard and it's paying off. I can't tell them how much I appreciate it.”
On a good day for KTM, test rider and Jerez wildcard Dani Pedrosa was sixth on another of the Red Bull RC16 machines.