Silva talked, taunted and dared Weidman to engage him. When the champion lowered his hands early in the second round, Weidman caught him with a short left that sent the MMA star to the mat. Weidman pounced and landed a few more shots that forced referee Herb Dean to stop the fight at 1:18.
"I felt destined for this," Weidman said. "It was far-fetched, but I imagined it so many times before in my head."
The win put an end to Silva's nearly seven-year reign atop the UFC middleweight division and his 17-fight win streak.
"I worked for this fight, Chris Weidman is the best now. He is the champion," Silva said. "I've had the belt for a long time. I'm tired."
The former champion fell to 33-5 with the loss.
"(Silva) was an idol of mine. I didn't want to mention it in the camp," said Weidman (10-0), who earned knockout of the night award. "I looked up to him for many years."
In the co-main event in front of a capacity crowd at the MGM Grand Garden in Las Vegas, former lightweight champion Frankie Edgar outwrestled and outstruck Charles Oliveira to get the win by unanimous decision.
Fighting in his first non-title fight in more than 3 1/2 years, Edgar looked sharp and utilized excellent footwork to avoid Oliveira. The first two rounds were close, but the third saw Edgar land a number of clean power punches and pull away for the win.
"I thought I had him hurt in the third, but he showed some toughness," said Edgar, who improved to 15-4-1 and placed himself in title contention with the win. Oliveira fell to 16-4.
On the main card, Mark Munoz and Tim Kennedy each earned unanimous decision victories and Cub Swanson bested Dennis Siver in a battle of highly ranked featherweights with a third round TKO.