Rodriguez belted a 2-0 pitch from Toronto's Shaun Marcum out to dead center field at Yankee Stadium in the first inning to accomplish the feat after a drawn-out pursuit of the milestone.
He had gone 12 consecutive games -- and 46 at-bats -- without a homer since hitting No. 599 on July 22 and entered the game mired in a 0-for-17 slump.
Rodriguez became the quickest player, by age, to reach 600 home runs, beating Babe Ruth to the mark by more than a full calendar year. Ruth was 36 years, six months and 15 days old when he crossed the 600-homer threshold. Rodriguez was 35 years and nine days old.
Ruth, Barry Bonds, Henry Aaron, Willie Mays, Ken Griffey Jr. and Sammy Sosa are the other members of the 600 home run club.
A New York crowd that has watched Rodriguez struggle to make solid contact lately, let alone hit a home run, gave him a raucous ovation as he rounded the bases. Rodriguez's teammates greeted him at the top step of the dugout before the third baseman stepped back up for a curtain call.
There was no frenzied scramble for the long-awaited home run ball, either. It came to rest in Monument Park, where a stadium security guard retrieved it.
The milestone homer came three years to the day after Rodriguez's 500th homer, hit at the previous incarnation of Yankee Stadium against the Royals.
FanHouse TV's Steve Phillips talks about A-Rod's next target after 600: