The Dutch giants fell to third place as a result and will drop into the Europa League, along with a some other big names in Europe.
Inter were also consigned to the second tier competition, courtesy of a 2-1 defeat to Barcelona, with Ansu Fati scoring the goal that sent the Italians out. The Barca phenom became the youngest goalscorer in the tournament’s history in the process.
The defeat at Amsterdam ArenA was the second of the campaign for the Eredivisie champions, having also gone down to a 1-0 defeat to Chelsea in October.
In that game Michy Batshuayi scored in the 86th minute to break Ajax hearts. Against Valencia they were unable to get back in the match after Rodrigo scored for the Spaniards after 24 minutes.
Ajax rained down 17 shots in the game, but could only direct three on target, the same as their opponent managed from eight total shots.
They must refocus immediately as a cruel schedule sees them face AZ on Sunday.
Ajax have a three point lead over AZ in the Eredivisie standings, but a defeat on Sunday would see them face the prospect of the winter break potentially level on points. Both teams have one more league game before the two-week interval.
Ajax won a lot of fans on their run to the semi-finals of the competition last season, but, having lost both Frenkie de Jong and Matthijs de Ligt over the summer some observers were unsure if they could ascend to the same heights.
Their campaign began well before the set back against Frank Lampard’s team, and a crazy 4-4 draw at Stamford Bridge derailed it somewhat.