That is, until now.
Rooney and Villa have been two of the world's best strikers for a decade, leading the lines for some of Europe's best teams every year while excelling internationally — both are the all-time leading scorers for their decorated countries.
Yet, somehow, they will line up against each other for only the second in their careers on Saturday (4:55 pm ET | Univision & Twitter - full TV & streaming info) when Rooney's D.C. United travel to Yankee Stadium to face Villa's New York City FC.
With United chasing playoff qualification and NYCFC looking to build momentum at the business end of the season, there's plenty at stake for their first meeting in MLS.
Their first ever meeting was a momentous occasion: Rooney's Manchester United and Villa's FC Barcelona played in the 2010-11 Champions League final at Wembley Stadium. Barcelona triumphed 3-1 as both current MLS stars made it onto the scoresheet that day.
Barcelona took the lead in the first half before Rooney equalized, via a brilliant one-two with Ryan Giggs. Lionel Messi pushed Barça ahead in the second half, then Villa put the game out of United's reach with a beautiful curling strike from some 22 yards out.
On the international stage, Spain and England never faced each other in an international tournament nor qualifying, though did play a handful of friendlies. Oddly enough, not once did both players feature in the same game.
Individually, Villa and Rooney have racked up the accolades. Between the two of them, they have a combined eight league titles, two Champions League medals, seven domestic cup triumphs and an excess of individual awards. Villa scored at least 15 goals or more across all competitions in 13 of the last 14 seasons, excluding this year. Rooney, who has spent less time as an out-and-out striker, has hit 15 goals or more in 11 of those 14 years.
Now, the two legends will start their MLS duel.
Villa made the move to MLS ahead of NYCFC's inaugural 2015 season, becoming the club's first-ever signing and first captain. Rooney joined the league this summer and has sparked D.C.'s playoff chase. Rooney has four goals and five assists in his first nine MLS games, while Villa has 10 goals in 17 appearances while battling injuries most of the season.
After Saturday, the pair won't have to wait nearly as long for their third career meeting, as NYCFC travel to Audi Field for the first time on Oct. 21, in the penultimate week of the regular season. And as fate may have it, they could meet in the Audi 2018 MLS Cup Playoffs just two weeks thereafter.
The great European rivalry that never was may finally get its due in MLS.