Yvonne worked as a teacher and Melvin worked variously as a scout for the Kansas City Royals, a mortgage broker and a college basketball referee in the Mid-Eastern Athletic Conference after playing both college football and basketball at Norfolk State.

[1][2] Before high school, Upton played on the same travel baseball team as several other MLB players, including Mark Reynolds, David Wright, and Ryan Zimmerman.

[5] In 2002, Upton was named a first-team All-American by Baseball America, batting .641 (50-for-78) with 11 doubles, four triples, 11 home runs, and 32 RBI during his senior year at Greenbrier.

His younger brother, Justin, was taken with the top overall choice of the 2005 Major League Baseball draft, making them the highest-drafted siblings of all time.

On June 8, Upton was forced to leave a game against the Florida Marlins early due to a strained left quadriceps.

He was one of only 6 batters in the AL to have at least 20 home runs and 20 stolen bases, along with Alex Rodriguez, Gary Sheffield, Ian Kinsler, Grady Sizemore, and Curtis Granderson.

During the 2008 season, Upton was twice disciplined by Rays manager Joe Maddon for lack of hustle.

[12] On August 15, Upton was benched in the sixth inning for not running out a double play ball.

[14] However, he would become one of the team's postseason heroes, as he hit 7 home runs in the three post-season series' Tampa Bay played in.

It resumed two nights later and the Rays lost the World Series to the Philadelphia Phillies, 4 games to 1.

[15] In 2009, he batted .241, his 42 stolen bases were third in the league (as he was caught a third-most 14 times), and his 152 strikeouts were fifth in the AL.[9] During the Rays' June 27, 2010, home game against the Arizona Diamondbacks, Upton took a long time to retrieve a ball hit by Rusty Ryal into left-center field, allowing a double to become a triple.

Maddon found fault with how hard Upton ran after the ball after Ryal pulled it into left center field.

[21] During the 2012–2013 offseason, Upton entered free agency where he signed a five-year, $75.25 million contract with the Atlanta Braves.

[26] On August 8, the Uptons both hit home runs in the same game for the fifth time, setting a new Major League record for brothers.

The Uptons previously shared the record for homering in the same game on four occasions with Vladimir and Wilton Guerrero and Jason and Jeremy Giambi.

On April 5, 2015, Upton was traded to the San Diego Padres along with Craig Kimbrel in exchange for Carlos Quentin, Cameron Maybin, outfield prospect Jordan Paroubeck, pitching prospect Matt Wisler, and the 41st overall pick in the 2015 MLB draft, which 2 months later turned out to be Austin Riley.

[31] Upton soon began making starts in center field, which had been primarily manned by Wil Myers and Will Venable earlier in the season.

Upton finished 2015 with a .259 batting average and five home runs in 87 games, including 47 starts in center field.

[9] On July 26, 2016, Upton was traded to the Toronto Blue Jays, along with cash considerations, for minor league pitcher Hansel Rodriguez.

Upton spoke with his family members about using his birth name full-time, before filing the paperwork with the Major League Baseball office.