The 1942–43 Wyoming Cowboys basketball team represented the University of Wyoming in NCAA men's competition in the 1942–43 season. The Cowboys won the Mountain States Conference championship and were the first basketball team from the Rocky Mountains to win an NCAA Basketball Championship. Kenny Sailors of Hillsdale, Wyoming averaged 15.5 points per game and Milo Komenich averaged 16.7 points per game in leading the team to the championship. Despite playing just nine home games during the year, the Cowboys won 32 games.
In the fourth game of the season, the Cowboys lost to Duquesne. It would be the last game the Cowboys lost to a college team during the season. Their only other loss was to the Denver Legion team. The Cowboys outscored their opponents by an average of over 20 points per game and that 1942–43 squad became the first Wyoming team to score over 100 points in a game, by beating Regis 101–45.
St. John's won the National Invitation Tournament that same year and claimed it was better than Wyoming and that the NIT was a better tournament than the NCAA. Ev Shelton talked Ned Irish, the promoter at Madison Square Garden, into hosting a showdown game, with proceeds going to the Red Cross. Two days after winning the NCAA Championship, Wyoming played NIT Champion St. John's in a Red Cross benefit game for the war effort. Wyoming beat St. John's in overtime by a score of 52–47, in Madison Square Garden.
Wyoming's championship may not have happened had the season not coincided with World War II. That same year, the Illinois Fighting Illini finished the season with a record of 17 wins and 1 loss. The season was cut short as all five starters headed off to active duty in the armed forces. Illinois won the Big Ten Conference Title and had finished the regular season as the nations' top ranked team. Due to military service, the club did not participate in either the NCAA or NIT tournament.