The striker had not featured for El Tri since 2011 but fired Miguel Herrera's men to a win over the Oranje, who slumped to their fourth defeat in five games since the World Cup
Carlos Vela ended his three-year international absence in style by scoring twice as Mexico got some revenge on Netherlands for their World
Cup elimination with a 3-2 victory on Wednesday.
Vela was making his first appearance for the national side for three and a half years at the Amsterdam ArenA after refusing several call-ups, with his unwillingness to play for his country seeing him miss the 2014 World Cup.
However, the Real Sociedad striker accepted the latest olive branch from Herrera and wasted no time in illustrating his worth with a well-taken double.
Vela's two goals were separated by a powerful volley from Wesley Sneijder on a night that saw the Galatasaray star become the third-most capped Netherlands player with 110 international appearances.
But Javier Hernandez added a third to render that moment of magic irrelevant in spite of Daley Blind's deflected 74th-minute strike.
Mexico stood firm to gain a measure of revenge for their 2-1 loss to Netherlands in the last 16 of the World Cup and place further pressure on Dutch head coach Guus Hiddink, who revealed that he would resign if his side lose to Latvia in Euro 2016 qualifying on Sunday.
Sneijder was presented with a pre-match award for reaching 100 caps, but it was Vela who stole the spotlight just eight minutes after kick-off as he marked his comeback with a magnificent goal.
Vela curled a superb 20-yard effort beyond a helpless Tim Krul and into the top corner, silencing the crowd at the Amsterdam Arena with his first goal since a 2-1 win over Italy in June 2010.
Hiddink was made to reshuffle in the 24th minute when centre-back Ron Vlaar was forced off through injury and replaced by Stefan de Vrij.
Despite that setback Netherlands began to take control of the game, Depay casually firing over from a clever lofted pass from the ever-threatening Robben, who worked Mexico goalkeeper Guillermo Ochoa with a powerful low drive from distance.
But the chance of the half fell to Klaas-Jan Huntelaar, the Schalke striker somehow firing wide at the far post with the goal at his mercy after De Vrij had nodded a Robben corner into his path.
However, only four minutes into the second half Sneijder levelled in spectacular fashion. The 30-year-old controlled a Mexico clearance brilliantly before unleashing an unstoppable dipping volley that left Ochoa groping at thin air.
Krul produced a fine point-blank save from Hernandez but the Newcastle United keeper turned from hero to villain in the 62nd minute, as he allowed Vela's half volley to sneak underneath him after his defence had been undone by substitute Jesus Corona clever pass.
And the visitors ultimately put the result beyond doubt seven minutes later when Hernandez latched onto a throughball from Andres Guardado, rounded Krul and tucked into an empty net.
Yet a touch of fortune gave the hosts a route back into the contest, Blind's long-range strike taking a wicked deflection that wrongfooted Ochoa to halve the deficit.
A night of frustration for Netherlands was encapsulated in the 85th minute when Ochoa dived to his left to keep out a header from substitute Georginio Wijnaldum, sealing a result that ramps up the strain on the shoulders of Hiddink ahead a qualifier that could see his second spell in charge of his country come to an early end.