Myers, a first-time All-Star in 2016, has agreed to a six-year extension with the Padres, club sources told ESPN's Jim Bowden.
Fox Sports, which first reported the agreement, says the deal is worth more than $80 million.
The deal is pending a physical. Myers, who primarily played first base in 2016, had been eligible for arbitration.
After battling injuries for two seasons, Myers, 26, stayed healthy for San Diego in 2016, appearing in 157 games and batting .259 with 28 home runs and 94 RBIs. That was his best season since 2013, when he hit .293 with 13 home runs and 53 RBIs in 88 games for the Tampa Bay Rays as a rookie.
The Rays traded Myers to the Padres in 2014.
Also Friday, third baseman Yangervis Solarte agreed to a two-year contract with San Diego that includes club options for the 2019 and 2020 seasons. Solarte had a career season in 2016, hitting .286 with 15 home runs and 71 RBIs.
The Padres also agreed to terms with left-handed starter Christian Friedrich and relievers Brandon Maurer and Brad Hand. Friedrich's deal is for $1.79 million, Maurer's for $1.9 million and Friedrich's for $1,375,000, according to multiple reports.
A lefty, Hand led the majors with a career-high 82 appearances. Maurer, a righty, set career highs in appearances (71), strikeouts (72) and saves (13).
Friedrich set career highs in nearly every pitching category in 2016, including starts (23), innings pitched (129.1) and strikeouts (100) while going 5-12 with a 4.80 ERA.
The Associated Press contributed to this report.