Fernando Llorente answered Raul with a brace of his own, and Oscar de Marcos and Iker Muniain also scored late as Athletic Bilbao downed Schalke, 4-2, on Thursday in Europa League action.
Raul, the all-time leading scorer in European competitions, erased an early Llorente goal within just a few minutes and added a spectacular volley early in the second half as Schalke took the lead at Veltins Arena.
But Llorente tied the match after 73 minutes, de Marcos followed in the 80th, and Muniain sealed a two-goal aggregate advantage with a goal 3 minutes into stoppage time.
Athletic Bilbao disposed of Manchester United in the last round, and takes four away goals back to Spain for the second leg against Schalke next week.
Fellow Spanish side Atletico Madrid also won its opening leg against German opposition, as Falcao and Eduardo Salvio trumped a goal from Mame Biram Diouf in a 2-1 win over Hannover at the Vicente Calderon.
Valencia, the third Spanish side in the quarterfinals, dropped its first leg at Dutch side AZ Alkmaar, 2-1. Brett Holman scored late in the first half for AZ and, after Mehmet Topal leveled for Valencia, Maarten Martens scored the winner in the 78th.
Sporting Lisbon used goals from Marat Izmailov and Emiliano Insua to win the first leg of its series against Ukraine side Metalist Kharkiv 2-1, but the visitors left Portugal with a key away goal on a last-minute penalty from Cleiton Xavier.
All four seconds legs are April 5.