He played in Major League Baseball (MLB) for the Tampa Bay Rays, Pittsburgh Pirates and Minnesota Twins.

He signed a letter of intent to attend the University of Miami, but decided to turn professional after high school.

[6] On December 31, 2008, Archer was traded, with John Gaub and Jeff Stevens to the Chicago Cubs for Mark DeRosa.

[13] After the season, Archer pitched for the United States national baseball team in the qualifying tournament for the 2011 Pan American Games.

[15] In January 2011, the Cubs traded Archer to the Tampa Bay Rays with Hak-ju Lee, Brandon Guyer, Robinson Chirinos, and Sam Fuld for Matt Garza, Fernando Perez, and Zac Rosscup.

[22] In his MLB debut, Archer allowed three hits and three runs (one earned) while recording seven strikeouts in six innings, becoming the first pitcher the Rays did not draft to start a game for the team since Matt Garza on September 30, 2010.

He recorded his first major league win on September 19, 2012, against the Boston Red Sox at Tropicana Field after going five innings and giving up three earned runs.

Among AL rookies, Archer ranked first in ERA, opponents' average (.226), complete games (two), shutouts (two), hits per nine innings (7.5) and WHIP (1.13).

Archer finished third in voting for AL Rookie of the Year, behind Detroit's Jose Iglesias and teammate Wil Myers.

Archer was named the Rays' Opening Day starter after Alex Cobb was placed on the 15-day Disabled List to begin the season.

Archer finished 5th in the American League Cy Young Award voting, behind Dallas Keuchel, David Price, Sonny Gray, and Chris Sale.

[35] Archer was a favorite among many baseball writers and fans to win the Cy Young Award before the season started after his strong 2015.

[38] After pitching in the World Baseball Classic, Archer received the nod as the Rays opening day starter.

[45] On July 31, 2018, Archer was traded to the Pittsburgh Pirates in exchange for Tyler Glasnow, Austin Meadows and a player to be named later, later revealed to be Shane Baz.

[46][47] In a game on April 7, 2019, against the Cincinnati Reds, Archer gave up a second-inning, two-run home run to Derek Dietrich.

[50] On October 31, 2020, the Pirates declined Archer's club option for 2021, making him a free agent for the first time in his career.

[58] On December 4, 2023, Archer took a job with the Los Angeles Dodgers as an assistant in their baseball operations department for the 2024 season.

[60] In his only start of the tournament, the first game for Team USA, Archer pitched four perfect innings against Colombia in a 3–2, extra-inning victory for the US.

[62] According to Pedro Martinez, Archer was prone to expose the ball too early, long before release, leading to batters getting clear clues to his pitches, and compounded by his slow release time compared to other right-handed low-three-quarters-position pitchers like Edinson Vólquez and Jacob deGrom.