Pittsburgh Pirates
On May 11, 2024, the Pirates selected Skenes' contract and promoted him to the major leagues for the first time. In his MLB debut at PNC Park against the Chicago Cubs that day, Skenes threw 17 fastballs at 100 miles per hour (160 km/h) or higher and struck out seven, but surrendered three earned runs in four innings in a no decision. In his second start, against the Cubs at Wrigley Field on May 17, Skenes threw six innings without allowing a hit, striking out eleven batters (including the first seven batters he faced).
On July 7, 2024, he was selected to the 2024 Major League Baseball All-Star Game, becoming the first No. 1 draft pick to do so as a rookie. On July 11, National League team manager Torey Lovullo named Skenes the starting pitcher for the National League for the game, becoming the fifth rookie ever to receive the selection. Skenes threw a scoreless inning in the All-Star game, walking Juan Soto but subsequently retiring Aaron Judge with a groundout.
On September 9 against the Miami Marlins, Skenes struck out Connor Norby in the top of the first inning to record his 143rd strikeout, the new Pittsburgh Pirates franchise record for strikeouts in a single season by a rookie. Skenes ended his rookie season with a 1.96 ERA, 0.95 WHIP, 170 strikeouts, 32 walks, and an 11–3 record in 23 starts. After the season, Skenes was named NL Rookie of the Year and finished third for the Cy Young Award losing to Chris Sale of the Atlanta Braves.
On January 28, 2025, Skenes was named as one of the three cover athletes of MLB The Show 25 alongside Elly De La Cruz and Gunnar Henderson, making him the first pitcher, excluding two-way player Shohei Ohtani, to be featured on an MLB The Show cover.
On March 27, 2025, Skenes was the Opening Day starting pitcher for the 2025 Pirates. Facing the Miami Marlins at LoanDepot Park, he pitched five1⁄3 innings, giving up two hits and walking two while striking out seven. However, the Marlins scored three runs in the last two innings off of Pittsburgh's bullpen, defeating the Pirates, 5–4, and leaving Skenes with a no decision. On April 2, 2025, he got his first win of the season against Tampa Bay Rays, pitched seven innings, giving up three hits, and striking out six batters in a 4–2 win. On April 26, 2025, Skenes hurled 61⁄3 scoreless innings and recorded a season-high with nine strikeouts in the Pirates’ 3–0 win against the Los Angeles Dodgers.
On July 6, Skenes was named to the 2025 All-Star Game roster, his second consecutive NL All-Star selection. On July 12, National League team manager Dave Roberts named Skenes the starting pitcher for the National League for the game, his second consecutive year to receive the selection. Skenes threw a scoreless inning in the All-Star game, striking out Gleyber Torres and Riley Greene and retiring Aaron Judge with a groundout. Skenes was named as National League Pitcher of the Month for July after posting a 3–2 record, 0.67 ERA, allowing 21 hits and two earned runs, striking out 36 batters, and walked three in 27 innings. It was the first time he earned Pitcher of the Month in his career. Skenes' 50 start on August 24 against the Colorado Rockies and he lowered his career ERA to 2.02. Since the start of the Live Ball Era in 1920, the only pitcher to have a lower ERA over their first 50 starts is Vida Blue, who recorded a 2.01 ERA from 1969-1972. On September 10, Skenes pitched five innings, giving up two hits, and striking out eight batters against Baltimore Orioles at Oriole Park at Camden Yards. With those eight Ks, Skenes recorded his first 200-strikeout season. He became the 8th Pirates pitcher in franchise history to strike out 200 batters in a season, joining Ed Morris, Bob Veale, Óliver Pérez, Mitch Keller, A. J. Burnett, Francisco Liriano, and Gerrit Cole. Skenes finished the season with a 1.97 ERA, the first sub-2.00 ERA for a starting pitcher since Justin Verlander's 1.75 ERA with the Houston Astros in 2022. He became the fourth player in the live ball era (since 1920) to record an ERA that low in his age-23 season or younger, joining Dwight Gooden (1985 at age 20), Vida Blue (1971, age 21), and Dean Chance (1964, age 23). He also set a new franchise record for most strikeouts for a right-handed pitcher, now sitting at 216 after breaking Mitch Keller's record of 210.
Named the opening day starter for 2026, Skenes allowed five runs in the first inning against the New York Mets on March 26, and was relieved of duties by the bullpen after recording only two outs. However, he quickly rebounded over the next 5 starts, winning 4 decisions and lowering his ERA back to a solid 2.48, with 30 strikeouts over 29 inning of work. He was particularly dominant against the rival Milwaukee Brewers, where he carried a perfect game into the 7th inning, before allowing a 2-out single to Jake Bauers. He eventually got the next out, pitching seven scoreless innings with 7 punchouts, to earn the win.
In July, he made the All-Star Game for a third consecutive year.
