On April 4, 1999, Castilla was a part of history as the Rockies played their Opening Day contest in his native Mexico at Estadio de Béisbol Monterrey in Monterrey. The game marked the first time Major League Baseball (MLB) commenced the regular season outside of the United States or Canada. The Rockies' opponent were the defending National League champion San Diego Padres. Castilla delighted the crowd with four hits including a double, as Colorado won 8–2..
On June 6, 1999, Castilla produced his first career three-home run game against the Milwaukee Brewers. His offensive numbers declined a little, hitting for a .275 batting average (first time in 5 years he didn’t eclipsed the .300 mark) He finished the season with 33 home runs, but for the 4th year in a row he had 100+ RBIs (102). He had the 3rd highest number of errors at third base with 19.