Miguel Layun scored a fortunate brace for Miguel Herrera's men, who face Brazil, Croatia and Cameroon at the FIFA World Cup.
Layun struck just before half-time and again in the 62nd minute with his first international goals helping Mexico stay unbeaten in 2014.
Marco Fabian added polish to the scoreline with his fifth goal at international level.
The game was also a tribute to the career of Cuauhtemoc Blanco, who started in attack to earn his 120th and final cap for the national team, while Manchester United striker Javier Hernandez played the second half.
Former Liverpool and Chelsea midfielder Yossi Benayoun came on in the second half for Israel, becoming the country's equal most capped player with 94 appearances.
In a concern for Herrera, goalkeeper Jose de Jesus Corona was stretchered off during the second half after a heavy collision with defender Francisco Rodriguez.
The visitors made a bright start and tested Corona in just the fourth minute, but on-loan Arminia Bielefeld striker Ben Sahar could only fire his shot from an angle straight at the goalkeeper.
Blanco received the loudest cheer as he got on the ball soon after, involved in the lead-up as Andres Guardado fired a 25-yard shot over the bar.
Israel, who mostly sat deep, looked dangerous on the counter-attack, but had a glorious chance from a set-piece in the 18th minute.
Maccabi Tel Aviv captain Sheran Yeini found space from a corner and needed to do better than head well wide of Corona's goal.
Oribe Peralta, left isolated up front, had a good chance midway through the half, but his shot lacked power and Israel goalkeeper Ariel Harush kept it out with his feet.
Blanco drew a foul soon after, only for the 41-year-old to take the free-kick and curl it well wide from 35 yards.
He made way to huge applause in the 39th minute, having scored 39 goals in his international career to be Mexico's second all-time leading goalscorer, and he did a lap of honour at half-time.
The hosts had looked unlikely to score and needed a bit of luck to go 1-0 ahead thanks to Layun two minutes before half-time.
Layun cut in from the left before firing a powerful 30-yard effort which went in after Harush missed with his attempted punch.
Hernandez's introduction at half-time gave Mexico more energy in the attacking third, but it was Israel who almost levelled in the 53rd minute as Rami Gershon headed a corner wide.
Layun doubled his and Mexico's tally just after the hour-mark.
The America man again tried his luck from distance and Harush appeared to have made a good save at full stretch, only for the ball to loop up and into the opposite corner.
Corona kept out a swerving Eran Zahavi free-kick moments later and Mexico enjoyed their best moments in possession late on.
They were rewarded in the 85th minute as Hernandez's shot from an angle deflected into the path of Fabian, who drilled in from inside the area and the United man – in an offside position – jumped over the strike.
Mexico have matches in the United States against World Cup sides Ecuador, Bosnia-Herzegovina and Portugal before heading to Brazil.
