Soto's 42nd of the year came in the bottom of the fourth inning off Washington Nationals relief pitcher PJ Poulin.
His previous single-season high in home runs - 41 - was set last year as a member of the New York Yankees. He needs to knock in seven more runs before the season ends to break his personal best of RBI in a season (109).
The Mets' right fielder also received a standing ovation from the fans in the bottom half of the inning when he went out to take his position.
Earlier this season, Soto became the first batter in Major League Baseball to hit for 30 home runs and steal 30 bases - the latter of which he more than doubled his career best.
The 26-year-old superstar signed a record-breaking 15-year, $765 million deal with the Mets this past offseason and is having a career year.
Heading into Friday's matchup against the Nats, Soto was slashing 263/.394/.528 while leading all of baseball with 119 walks. His 116 runs place him in third in all of baseball, needing 17 more to set a new career high.
So, in all, Soto could set a career high in runs, home runs, RBI, and stolen bases in the same year after signing his new deal.
The Mets (79-74) have just eight games left after Friday for Soto to pull it off, as they will do all they can to hold that third Wild Card spot in the National League.