There was little for De Boer to enjoy in a largely one-sided friendly at Johan Cruijff Arena, where Tata Martino's high-energy team made it 18 wins from their past 19 matches as Netherlands debuts for Owen Wijndal and Teun Koopmeiners fell flat.
De Boer indicated before the game that he would rather have had extra time to prepare for his side's forthcoming pair of Nations League matches than play a friendly, but he had to watch as the Netherlands were pulled apart at the back repeatedly as Raul Jimenez and Jesus Corona caused them problems.
There were chances at either end, with Memphis Depay lively in the Dutch attack, but a second-half Jimenez penalty after he was fouled by Nathan Ake settled the game and ensured De Boer's tenure started with a whimper.
4 – The Netherlands recorded just four touches in the opposition box in the first half against Mexico, their lowest tally in a single half since June 2019 (4 v Portugal). Toothless. pic.twitter.com/gscCcU0fjO— OptaJohan (@OptaJohan) October 7, 2020
Mexico exposed frailties in the Dutch defence early on when Hans Hateboer's slow reactions allowed Jesus Gallardo to put Jimenez clean through on goal, but the Wolves forward dragged his shot wide from 12 yards out.
Steven Berghuis' angled drive from close range stung the palms of diving Mexico goalkeeper Alfredo Talavera as the previously sluggish Netherlands began to rally.
But the visitors squandered another fine chance after 34 minutes when Wijndal's scuffed pass allowed Rodolfo Pizarro into the box where he squared to Jimenez, who fired low and wide again.
Tim Krul was called into action 10 minutes into the second half when Corona bore down on goal and the Netherlands keeper parried his low shot away from danger.
Moments later, substitute Ake was adjudged to have pulled Jimenez's shirt in the box as the referee awarded a penalty that the striker rolled into the bottom-left corner of the net.
Corona should have doubled Mexico's lead 15 minutes from time after his jinking run towards goal and fierce angled drive but Krul got down well to save.
Luuk de Jong had a late chance saved, too, before Memphis Depay hit the bar from the rebound, with neither able to spare De Boer's blushes.
What does it mean? De Boer critics emboldened
De Boer's appointment as Ronald Koeman's replacement did not sit well with some Netherlands fans, whose doubts over his pedigree and his ability to turn this team into one capable of competing at major tournaments could only have increased here.
Dutch struggle to contain Corona
Porto forward Corona was a constant threat for the visitors, providing Jimenez with a dynamic partner on the right of Mexico's attack where he enjoyed plenty of space in which to work. He had four shots - the most of any player on either side.
Torrid debut for Wijndal
Neither of De Boer's debutants impressed but it was a particularly tough night for 20-year-old AZ defender Wijndal, who made a glaring first-half error and was repeatedly beaten for pace by Corona. He did make five tackles, however, second only to fellow new boy Koopmeiners.