Mayberry played high school baseball in Kansas City, and USA Today named him a first-team 2002 All-USA player.

In 2005, Mayberry was rated by Baseball America as the Best Athlete and Best Outfield Arm among all Texas Rangers minor leaguers.

He returned to the major league squad in 2010 as a September callup, and remained there, with the exception of a short stint in Triple-A in 2011.

He remained with the big-league club in 2012, and played predominantly in left field early in the season, and subsequently as the team's everyday center fielder.

His father, John Mayberry Sr., a first round draft pick, himself (1967, 6th overall), played in MLB for over a decade, hitting over 20 home runs in eight separate seasons, and was a two-time American League (AL) All Star.

[1] His father, a two-time All-Star first baseman, played Major League Baseball for 15 seasons (1968–82) with the Houston Astros, Kansas City Royals, Toronto Blue Jays, and New York Yankees.

[7] During the summer of 2003, he also played for the Yarmouth-Dennis Red Sox of the Cape Cod Baseball League, batting .375.

[2] In 2004, he played with Team USA at the FISU World University Baseball Championship in Taiwan, winning a gold medal.

[7] He was rated by Baseball America as the Best Athlete and Best Outfield Arm among all Texas Rangers minor leaguers.

[6] He was rated by Baseball America as the Best Power Hitter, Best Athlete, and Best Outfield Arm among all Texas Rangers minor leaguers.

[17] For the season, Baseball America named him the fifth-best prospect in the Rangers' farm system, up from tenth in 2006.

The next day, in his first major league game, Mayberry got his first career hit, a three-run home run off of Andy Pettitte of the New York Yankees.

[25] After his second brief stint of the year in the minor leagues, he returned to the Phillies when left fielder Raúl Ibañez went on the 15-day disabled list with a strained groin.

Mayberry promptly proceeded to hit another home run in his return to the majors, this time off of Dirk Hayhurst of the Toronto Blue Jays.

[26] Several years later, a piece in The Philadelphia Daily News commented, "He has always had the physical tools that cause an organization to dream, as the Rangers did when they selected him in the first round in 2005.

But by 2009, that dream had been replaced by what they thought was reality: his swing was too long, his eye indiscriminate, his on base percentage low.

[28] He did earn a September callup, and "made a case" to have a place on the Phillies' postseason roster, but was assigned to the Mesa Solar Sox of the Arizona Fall League (AFL) instead.

In August, columnist David Murphy wrote, "While the Phillies may not see evidence that Mayberry should be part of their everyday plans, it is getting hard to ignore the two huge offensive tools he brings to the table: immense power, and a curious ability to hit when it counts."

[33] He finished the season batting .273/.341/.513, with a .854 OPS and 15 home runs in 104 games, and made his postseason debut in the National League Division Series against the St. Louis Cardinals that September.

A season-in-review article from SBNation.com opined, "(His) adequate defense at all three outfield positions makes him a decent fourth outfielder/bench bat, but at age 29 in 2013, the time for hoping that Mayberry finally puts his significant physical and intellectual gifts together to become an above-average Major League Baseball player appear to have gone completely.

"[38] Mayberry entered the season looking to bounce back from a rather tumultuous 2012 campaign, and was considered a solid bench player who can make occasional starts in the outfield.

Baseball statistician Bill James projected Mayberry would hold a .257 batting average and hit 11 home runs in 306 plate appearances.

Bill Baer, a writer for Crashburn Alley, a Phillies blog sponsored by ESPN, countered, "Everything Amaro said there is accurate.

[47] Mayberry entered the season a member of the Phillies bench who some writers thought was not worth his salary, but made the opening day roster.

[50] This success led some to suggest the Mayberry would have value in a potential trade, as the Phillies were not expected to make the playoffs, and thus might prefer to get a prospect for future seasons.

[53] On August 31, 2014, Mayberry was traded to the Toronto Blue Jays for minor league infielder Gustavo Pierre.

[54] He made his debut for Toronto on September 4, when he was put into the game against the Tampa Bay Rays to pinch-hit for Adam Lind.

[61] On January 13, 2016, the Detroit Tigers signed Mayberry to a minor-league $1 million contract and invited him to spring training.