In short, yes.

The most common cases of non-politicians being nominated are war heroes. There are three examples of popular generals who were elected President without previous political experience, and another with nearly none. Eisenhower retired from the military directly to run for the nomination, and Grant and Taylor actually served through the election, up until their inaugurations. And, of course, George Washington, although he had briefly been a delegate to the Continental Conventions, made his reputation almost entirely as a general and was elected unanimously; although he technically doesn't fit the bill of your question, since there were no political parties to nominate him.

There are also three examples of generals who were nominated and lost: Winfield Hancock, the 1880 Democratic nominee, was in the service at the time of his nomination and had never held elected office. George McClellan, who was removed from command by Lincoln in 1862, was nominated by the Democrats to run against him in 1864. And Winfield Scott, the Whig nominee who lost to Franklin Pierce in 1852, served a rather astonishing 53 years in the Army.

Alton Parker, who was nominated by the Democrats to run against Teddy Roosevelt in 1904, was then Chief Justice of the New York Court of Appeals, an elected position but technically not a political one.

In an example perhaps more in the spirit of your question, Wendell Willkie was nominated in 1940 with no public service experience whatsoever. A lawyer and partner in a private utility in the Tennessee Valley, Willkie had largely made his name in the political and legal struggle to prevent FDR's New Deal government monopoly over electricity generation in that region.

To get any more examples you have to stretch the definition of "major party". Ross Perot, who had no political experience, got over 8 million votes in 1996 and nearly 20 million in 1992. Eugene Debs, who got nearly a million votes in more than one election as the Socialist candidate, had been a political activist for years but was never elected. EDIT: Oops. Debs was in fact elected to a single term in the Indiana General Assembly, before he was a Socialist leader or in fact even a socialist.