Hamilton, who needs to finish only fifth in Sunday’s race to secure the 2017 drivers’ championship, struggled to get within half a second of his sole title rival Vettel around the Autodromo Hermanos Rodriguez.
“I gave it everything I could,” said the Briton. “It just wasn't the cleanest of sessions and they were quicker. The car on balance I think was fine, but we needed more.
“I think that last lap could have been a couple of tenths quicker, but still I wouldn't have been able to match these guys.”
Hamilton has said he would like to seal his fourth title with a win, but denied suggestions that he might end up taking risks in order to make that happen in Mexico, where the start is often the best chance to make up places.
“At the moment there is no risk to take,” he insisted. “If I get a good start and gain a position I will go for it, but at the moment that is an unknown.
“You need a 1.4s delta I think it is to the car in front to overtake, so it's going to be a train, but I get a good start, if I'm able to be close enough in the pit stop, who knows.”
With Hamilton’s team mate Valtteri Bottas all but matching his time in fourth place, Head of Mercedes-Benz Motorsport, Toto Wolff, said he was not unhappy with their performance given the characteristics of the Mexican circuit.
“We knew it would be a difficult circuit for Mercedes – our downforce isn't the best,” he commented. “I'm actually quite satisfied, quite pleased with the result.
“You need to take it weekend by weekend in order to improve the car and the performance for next year, and for sure we've done a step closer to Red Bull and Ferrari on the high-downforce track and that is satisfying.”
Mercedes have won both Mexican Grands Prix since the country rejoined the F1 calendar, with Nico Rosberg in 2015 and Hamilton last year.