He had a 10–1 win–loss record with a 0.80 earned run average (ERA) and 115 strikeouts and was named all-state by the North Carolina Baseball Coaches Association.

In 2011, he went 11–0 with a 1.40 ERA and 135 strikeouts, leading Holly Springs to the North Carolina 4A state championship over national powerhouse T. C. Roberson High School.

[6][7] In addition, he was a finalist for the Golden Spikes Award[8][9] and was named the Louisville Slugger's National Freshman Pitcher of the Year.

[3] He led the ACC in ERA (1.57), innings pitched (114+2⁄3), complete games (2), and opponent's batting average (.176), finishing second in the conference and third nationally in strikeouts.

He had 184 strikeouts, leading NCAA Division I; the prior four pitchers to lead the Division with that many strikeouts, three of whom were future major league Cy Young Award winners, were Tim Lincecum, David Price, Stephen Strasburg, and Trevor Bauer.

[16] He broke the NC State school record for career strikeouts, which had previously been 386, during an April 11, 2014, game against the Duke Blue Devils.

Originally, he almost turned down the offer because his coach at North Carolina State University, Elliott Avent, wanted to shut him down for the summer.

In two seasons on Team USA, Rodón was 5–0, allowed only three earned runs over 36 innings (0.75 ERA), and contributed 42 strikeouts.

[19] The Chicago White Sox selected Rodón in the first round, third overall, in the 2014 Major League Baseball draft.

[24] The initial plan was for Rodón to pitch out of the bullpen, the way Chris Sale began his major league career with the White Sox.

[25] He recorded his first start, and his first win, in the second game of a May 9 doubleheader against the Cincinnati Reds at US Cellular Field, giving up two earned runs in six innings on four hits, four walks, and eight strikeouts.

With the 2020 Chicago White Sox, Rodón appeared in 4 games, compiling an 0–2 record with 8.22 ERA and 6 strikeouts in 7+2⁄3 innings pitched.

[38] On March 14, 2022, Rodón signed a two-year, $44 million contract with the San Francisco Giants, containing an opt-out clause after the first season.

[40] On April 15 at Progressive Field, in a 4–1 win over the Cleveland Guardians, Rodón won his first start as a Giant by striking out nine batters over seven innings while allowing only two hits.

His 21 strikeouts broke Marichal's team record in the San Francisco Era for the most by a Giants pitcher in two appearances to start a season.

On July 12, 2022, Rodón was named as the MLB All-Star Game roster replacement for Josh Hader.

[45] On September 9, 2022, at Wrigley Field, Rodón struck out 11 Chicago Cubs batters, reaching double-digits in strikeouts for the 10th time that season.

This set a new Giants all-time single season franchise record, previously held by Tim Lincecum and Jason Schmidt.