A first baseman, Nen appeared in 367 games in Major League Baseball (MLB) for the Los Angeles Dodgers (1963), Washington Senators (1965–1967, 1970) and Chicago Cubs (1968).

After two years with Triple-A Spokane, the first-place Dodgers recalled him in September 1963 during the height of the National League pennant race.

In his major league debut September 18, 1963, he was inserted into the lineup as a pinch hitter in the top of the seventh inning against the second-place St. Louis Cardinals at Busch Stadium and lined out to centerfield off Bob Gibson, the future Hall of Famer.

Facing right-handed relief pitcher Ron Taylor, Nen hit a game-tying home run "over the roof" in right field[1] to send the game into extra innings.

Traded to Washington that December in a blockbuster deal headlined by Frank Howard and Claude Osteen, Nen spent the bulk of his MLB service time with the Senators, getting into 279 games and hitting 18 of his 21 big-league home runs with them.