Brooklyn Nets (2013–2015)
Plumlee was selected with the 22nd overall pick by the Brooklyn Nets in the 2013 NBA draft. On July 3, 2013, he signed his rookie-scale contract with the Nets. On November 15, 2013, in his first game against his brother Miles and the Phoenix Suns, he recorded 7 points, 3 rebounds and 2 assists in a 100-98 overtime win. The following night, Plumlee played 26 minutes against the Los Angeles Clippers with both Brook Lopez and Kevin Garnett out injured, and had 19 points and 6 rebounds, both career highs. Plumlee was selected to play in the 2014 BBVA Rising Stars Challenge on Chris Webber's team, while his brother Miles was picked to play on Grant Hill's team. On February 9, 2014, Plumlee recorded his second NBA double-double, finishing with 22 points and 13 rebounds in a Nets victory. On March 17, 2014, both Miles and Mason Plumlee started for the Suns and the Nets, respectively. Mason had 14 points and 11 rebounds, while Miles had 3 points and 6 rebounds in a 108-95 Nets win.
On April 8, 2014, the Nets faced the two-time defending champion Miami Heat, looking to become the first team to sweep LeBron James in a four-game season series. With Kevin Garnett resting his back and Andray Blatche out with illness, Plumlee was the only active center on the Nets roster. The Nets held an 88-87 lead in the closing seconds when James attempted a dunk that would have won the game for the Heat. Plumlee blocked the shot and secured the season sweep in what the New York Times described as a signature moment in his career. Although James was visibly upset about the play, and claimed that he had been fouled, the NBA later announced that the call was correct and that the block was clean. In 70 games (22 starts), he averaged 7.4 points and 4.4 rebounds per game as he earned NBA All-Rookie first team honors, becoming the first Net since Brook Lopez (2008–09) to earn such honors.
Following the departure of Andray Blatche, Plumlee came into the season as the primary back-up to Brook Lopez. On October 24, 2014, the Nets exercised their third-year team option on Plumlee's rookie scale contract, extending the contract through the 2015–16 season.
After starting the first two games of the season in the absence of Lopez, Plumlee moved back to a bench role in the wake of Lopez's return until the starting center once again missed time during December, in which Plumlee was put back into the starting line-up. He subsequently scored a season-high 18 points and added 10 rebounds on December 12 in helping the Nets defeat the Philadelphia 76ers, 88–70. He surpassed his season high on December 23 with 19 points, while also grabbing a career-high 13 rebounds, in a 102–96 win over the Denver Nuggets. On January 12, 2015, he surpassed his season high again with a career-high 24 points in a 113–99 loss to the Houston Rockets.
Portland Trail Blazers (2015–2017)
On June 25, 2015, Plumlee was traded, along with the draft rights to Pat Connaughton, to the Portland Trail Blazers in exchange for Steve Blake and the draft rights to Rondae Hollis-Jefferson. On September 30, the Trail Blazers exercised their fourth-year team option on Plumlee's rookie-scale contract, extending the contract through the 2016–17 season. On December 14, he recorded 15 points, 13 rebounds and a then career-high six assists in a 105–101 win over the New Orleans Pelicans. On January 6, he scored a season-high 19 points in a loss to the Los Angeles Clippers. On January 18, he recorded his 12th double-double of the season with 10 points, 11 rebounds and a career-high seven assists in a 108–98 win over the Washington Wizards. On January 29, in a win over the Charlotte Hornets, Plumlee recorded 13 points and 12 rebounds for his career-high 13th double-double of the season. On March 20, he recorded 14 points and a then career-high 19 rebounds in a 132–120 overtime loss to the Dallas Mavericks.
In Game 3 of the Trail Blazers' 2016 first-round playoff series against the Los Angeles Clippers, Plumlee recorded career highs of 21 rebounds and nine assists in a 96–88 win. He became the first player with 19 or more rebounds and eight or more assists in a playoff game since LeBron James in 2010. He also became the first Blazer center with eight-plus assists in a postseason game since Arvydas Sabonis in 1999. In Game 4 of the series, Plumlee recorded 14 rebounds, 10 assists, three blocks and two points in a 98–84 win, tying the series at 2–2.
On December 7, 2016, in a loss to the Milwaukee Bucks, Plumlee became the fastest Portland player to tally 150 rebounds and 100 assists (23 games) since Scottie Pippen in 1999–2000 (22 games). On January 8, 2017, Plumlee recorded eight points, a career-high 12 assists, 10 rebounds, three blocks and one steal across 40 minutes in a 125–124 double-overtime loss to the Detroit Pistons. His 10 rebounds and 12 assists made him the first Blazers forward or center to have a double-double in those categories since Mychal Thompson in January 1984.
Denver Nuggets (2017–present)
On February 13, 2017, Plumlee was traded, along with a 2018 second round draft pick and cash considerations, to the Denver Nuggets in exchange for Jusuf Nurkić and a 2017 protected first round pick.
On September 20, 2017, Plumlee re-signed with the Nuggets. After the death of Kobe Bryant in January 2020, Plumlee decided to change his jersey number from 24 to 7 to honor Bryant, who wore the number 24 during the final ten seasons of his career.
National team career
Plumlee was a member of the United States national team that won the gold medal in the 2014 FIBA Basketball World Cup. He also won silver with the Under-18 team at the FIBA Americas Under-18 Championship in 2008.