Valencia joined holders Barcelona, Real Madrid, Atletico Madrid and Sevilla, who gained an automatic berth as last season's winners of the second-tier Europa League.
On a night of pulsating action, Malmo, Dinamo Zagreb, Maccabi Tel Aviv and Shakhtar Donetsk also booked money-spinning group stage spots in Europe's premier club competition.
Swedish title holders Malmo advanced for a second successive season after Markus Rosenberg and a Dedryck Boyata own goal gave them a 2-0 home win over Celtic which a overturned a 3-2 first leg deficit.
Croatians Dinamo qualified for the third time in the past five seasons, beating Skenderbeu 4-1 at home to complete a 6-2 overall victory over the Albanians.
A nervy 2-2 home draw with Rapid Vienna saw Shakhtar through after a 1-0 win in the first leg while Maccabi edged out Basel on away goals, a 1-1 home draw being just enough following last week's 2-2 tie in Switzerland.
The top match of Wednesday's action features Manchester United's visit to Bruges, where the three-time winners will defend a 3-1 first leg advantage over the Belgians.