[2] Napoli began his professional career with the rookie-level Butte Copper Kings, batting .231,[3] but sat out most of the year after suffering a lower back strain.

[1] Napoli began 2007 as the Opening Day starting catcher, and split time with José Molina through the first half of the season.

[1] Napoli again was the Angels' Opening Day starter at catcher, and after recovering from his 2007 injuries, began the 2008 season by hitting six home runs in April.

Napoli continued to share time behind the plate with Jeff Mathis, who had assumed the back-up duties after the Angels' trade of Molina during the 2007 season.

However, after recovering from the injury, Napoli led all of Major League Baseball with a .457 batting average in the month of September.

Napoli set or matched career highs in games played (114), at bats (382), runs scored (60), hits (104), doubles (22), and RBIs (56).

[1] In 2010, the Angels reduced Napoli's playing time at DH after signing Japanese slugger Hideki Matsui.

[7] Napoli went into spring training with a bigger glove and worked on fundamentals in hopes of getting more playing time as a catcher.

He made his first major league start at first base on May 30, after regular first baseman Kendrys Morales broke his lower leg in a walk-off celebration.

With the loss of Morales for the season, and the return of fellow catcher Jeff Mathis from the disabled list, Napoli started 70 games at first base, posting a .989 fielding percentage, as he was fifth in the AL with six errors.

[10] Four days later, he was traded by the Blue Jays to the Texas Rangers in exchange for pitcher Frank Francisco.

[11] On May 29, Napoli was involved in a controversial game-ending play at home plate in the ninth inning in a game against the Kansas City Royals.

[1] In Game 5 of the 2011 World Series, Napoli hit a two-run double in the bottom of the eighth inning to give the Rangers a 4–2 lead.

He received the second highest raise for anyone in their third or fourth time through the arbitration process, with Prince Fielder taking the top spot.

[12] On December 3, 2012, Napoli agreed to a three-year, $39 million deal with the Boston Red Sox, pending a physical examination.

Upon his strikeout, Napoli threw his bat and helmet in frustration and argued with home plate umpire Ron Kulpa and was ejected for the first time in his Major League career.

For the 2013 season, Napoli batted .259 with 23 home runs, 92 RBI, and struck out 187 times, fourth-most in the AL and the most ever by a Red Sox player.

[1] After six games against the St. Louis Cardinals, Napoli received his first career championship ring as the Red Sox won their eighth World Series.

[1] On August 7, 2015, the Texas Rangers acquired Napoli from the Red Sox for a player to be named later or cash considerations.

[citation needed] He played 35 games for the Rangers in 2015, making 91 plate appearances and batting .295 with five home runs, 10 RBI and a .513 SLG.

[1] In game three of the 2016 American League Championship Series, Napoli's home run off Blue Jays starting pitcher Marcus Stroman made him the fifth player to hit a postseason home run for four different teams, joining Ron Gant, John Olerud, Reggie Sanders, and Russell Martin.

He was released on March 22 in a procedural move to allow the Indians to avoid having to pay him a $100,000 retention bonus.