Two goals from Radamel Falcao and further strikes from Miranda and Adrian Lopez gave Atletico a commanding lead over their Spanish rivals ahead of the second leg.
The hosts started brightly and could have been ahead even earlier as Diego Alves saved from Diego and Adrian before the latter showed great persistence to set Falcao up for the easiest of headers to open the scoring on 18 minutes.
After that initial burst from Atletico though, Valencia started to gain a foothold in the game and equalised in first-half stoppage time as Jonas swept home Adil Rami's knockdown.
However, 2010 Europa League winners Atletico started the second period in even stronger fashion and scored twice in nine minutes as Miranda took advantage of some slack marking to head home Diego's free-kick before Adrian slotted past Alves from a narrow angle.
Falcao looked to have all but sealed Atletico's place in the final in Bucharest with a sensational strike from outside the area that went in off the bar 12 minutes from time, but Ricardo Costa headed home from another corner with virtually the last touch of the game to give Valencia some hope heading into the return leg at the Mestalla next week.
Atletico's fast starts at home have been a feature of their run to the semi-finals and they pinned Valencia back in the opening stages.
Firstly, Arda Turan wriggled free on the right and his cut-back should have been dispatched from inside the area by Brazilian Diego, but he placed his shot too close to his compatriot Alves and he palmed the ball to safety.
Adrian then also shot straight at the former Almeria keeper, but Atletico deservedly took the lead when Adrian capitalised on Rami's dawdling to cut the ball back from the by-line and Falcao nodded home his ninth goal in Europe this season.
Valencia's first serious attempt on goal did not come until after the half-hour mark but it proved to be a warning the Atletico defence did not heed as Rami rose highest to head Tino Costa's corner just wide.
Jonas fired just over after Roberto Soldado had led a lightening quick counter-attack but moments later the Brazilian did have the away goal Valencia craved as he bundled the ball home at the back post after Rami had won another header from a Costa corner.
Unai Emery's men were only level for three minutes after the interval though as Miranda was left in acres of space from Diego's floated free-kick to easily nod past Alves.
And the home side had a two-goal cushion soon after as Mehmet Topal carelessly gave the ball away in midfield and Adrian pounced to fire low past Alves.
The Valencia keeper was called into action on three occasions to keep his side in the tie as he made a brilliant double save to deny Filipe Luis and Arda before turning Diego's free-kick over.
However, there was absolutely nothing Alves could do to stop Falcao's second with in the 78th minute as the Colombian broke the offside trap, turned inside onto his left foot and crashed a wonderful strike in off the underside of the bar.
Atletico, though, continued to defend set-pieces in a poor fashion as Costa was left all alone to head home deep into stoppage time to keep Valencia just in the tie.