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.

The Upton brothers competed on travel teams with Mark Reynolds, David Wright, and Ryan Zimmerman.

[citation needed] On August 2, 2007, Upton was called up to the big league team at the age of only 19, following an injury to everyday right fielder Carlos Quentin.

Despite a relatively disappointing start to his career (albeit with limited playing time), he broke out in the 2007 post-season, leading the Diamondbacks to a three-game sweep of the Chicago Cubs, making it to the NLCS.

[7] In 2008 spring training, Upton hit over .300 with three home runs, 12 RBIs, and four stolen bases, earning the starting right field job over Jeff Salazar.

[8] Upton began the season and held the current title of being the youngest active major leaguer second to Clayton Kershaw as of July 31, 2008.

In the sixth inning of a game against the Cincinnati Reds, he broke up a no-hitter in the major league debut of Johnny Cueto with a home run.

[citation needed] On July 5, Upton was named to the 2009 All-Star team as a reserve outfielder for the National League.

[citation needed] On August 5, 2009, against the Pittsburgh Pirates, Upton strained his right oblique trying to steal second base, resulting in a stint on the disabled list.

[11] Upton led the Diamondbacks in batting average (.300) and hits (158) to go along with 26 home runs (including his first career grand slam on 6/2/09 against the Dodgers) and 86 RBI.

[18] Through 2011, Upton was 2nd all-time of Diamondback hitters in HBP (30), 3rd in slugging percentage (.487) and OPS (.845), 4th in OBP (.357) and strikeouts (573), and 5th in triples (24).

[19] He came in fourth in the voting for the 2011 National League Most Valuable Player Award, behind winner Ryan Braun, Matt Kemp, and Prince Fielder.

[22] On January 20, 2013, the Arizona Diamondbacks traded Upton and Chris Johnson to the Atlanta Braves in exchange for Martín Prado, Randall Delgado, shortstop prospect Nick Ahmed, pitching prospect Zeke Spruill, and minor league first baseman Brandon Drury.

[24] The First time Melvin and Justin homered in the same game was April 6, 2013, when Melvin hit a game-tying home run off Carlos Marmol in the 9th inning and Justin Upton hit a game-winning home run (also off Marmol in the 9th inning) to lead the Braves a 6–5 victory over the Cubs.

[citation needed] On August 8, 2014, Justin and Melvin homered in the same game for the fifth time, setting a new Major League record for brothers.

The Uptons previously shared the record of four with two pairs of brothers: Vladimir and Wilton Guerrero, and Jason and Jeremy Giambi.

[29] On October 23, 2015, Upton, along with Starling Marte and Christian Yelich, was selected as a Gold Glove finalist in left field.

At the time of his selection, Upton was hitting .271 with 21 doubles, 15 home runs, 54 RBIs, a .356 on-base percentage, and a .384 batting average with runners in scoring position (ranking third in the AL).

[39] On September 15, the trade was completed with the Tigers acquiring Angels pitching prospect Elvin Rodríguez as the PTBNL.

[40] Upton finished 2017 with a .273 batting average and .361 on-base percentage, while setting career highs with 44 doubles, 35 home runs, 109 RBI, and a .901 OPS.

Upton was named a 2017 Gold Glove finalist in left field, along with Brett Gardner of the Yankees and Alex Gordon of the Royals.

[46] On March 24, 2019, during a preseason game against the Los Angeles Dodgers, Upton suffered a turf toe injury.

Upton finished the season batting .215/.309/.416 with 12 home runs and 40 RBIs, playing in just 63 games with a total of 256 plate appearances.

[citation needed] On August 27, 2021, against the San Diego Padres, Upton hit a sacrifice fly for his 1,000th career RBI.

On July 22, the Mariners optioned Upton to the Triple–A Tacoma Rainiers, but he refused the assignment and elected free agency.