The US secret service, which provides security for presidential candidates, later said someone in the crowd had shouted “gun” but no weapon was found.
Mr Trump returned to continue his speech a short time later, and the suspect wrestled to the ground during the incident and frogmarched from the venue was released.
Austyn Crites, who carried out the protest, said: “I am actually a Republican, I just don’t support Donald Trump.”
He added: “I am doing what I believe is my democratic duty to show that even though we are from the same party, even though a lot of the things that he says may resonate with a lot of people…I just believe he’s very dangerous for the country.
“I just came with a sign, I literally had one sign that said ‘Republicans against Trump’.”
Mr Trump reappeared just minutes after being bundled from the hall mid-speech by secret service agents, shielding his body with their own.
:: Trump: Made In America – a Sky News special programme on the Republican Party candidate – at 4pm on Sunday
Shortly before the incident, the 70-year-old Republican tycoon could be seen sheltering his eyes from the lights in order to peer into the crowd.
As he was led away there were signs of a scuffle in the audience before police intervened.
Mr Crites was held face down on the ground while officers searched him and there was booing as he was led from the venue.
Returning to cheers, Mr Trump said: “No one said it was going to be easy for us, but we will never be stopped, never ever be stopped.”
The candidate also thanked the secret service agents.
He said: “These guys are fantastic. They don’t get enough credit. They don’t get enough credit. They are amazing people.”
The secret service said in a statement later: “Mr Trump was removed from the stage by his secret service protective detail after a commotion occurred in the crowd.
“Immediately in front of the stage, an unidentified individual shouted ‘gun’. Secret service agents and Reno police officers immediately apprehended the subject.
“Upon a thorough search of the subject and the surrounding area, no weapon was found.”
The false scare came Mr Trump and his Democratic rival Hillary Clinton stepped up their campaigns in the countdown to Tuesday’s vote after one of the most bitterly fought and tumultuous presidential races of all time.
Mr Trump used his speech in Reno to argue Mrs Clinton should not be allowed to run for president while the FBI continued its investigation into her use of a private email server for work correspondence while she was US secretary of state.
He told supporters: “We need a government that can work, and work well from day one for the American people.
“That would be impossible with Hillary Clinton, the prime suspect in a massive far-reaching criminal investigation.”
Meanwhile, Mrs Clinton continued her bid to make history by becoming America’s first woman president.
She has secured the backing of A-list celebrities to her campaign including Katy Perry, Beyonce and Jay Z.
Perry, wearing a purple cape with the words “I’m with Madam President”, told a rally: “In three days, let’s make history.”