Ryan left Houston after a contract dispute following the 1988 season and signed with the Texas Rangers at age 42. He became the first player to play for all four MLB original expansion teams: the Mets, Angels, Houston Colt .45s/ Astros and Washington Senators/Texas Rangers. (Ryan was joined in this category by Darren Oliver, who made his major league debut as Ryan's teammate in September 1993. Oliver's father Bob had also been a teammate of Ryan's, with the Angels from 1972 to 1974.) In 1989, he went 16–10 and led the league with 301 strikeouts. Against the Oakland Athletics on August 22, Ryan struck out Rickey Henderson to become the only pitcher to record 5,000 career strikeouts. (Following the game, Henderson was quoted as saying, "If he ain't struck you out, then you ain't nobody.") His 4,999th and 5,001st strikeouts were against the same man, Athletics catcher Ron Hassey. Two years later, at 44, Ryan finished fifth in the league in ERA (2.91) and third in strikeouts (203).
Before the 1993 season began, Ryan announced that he would retire as a player at the end of that season. On August 4, just before the end, Ryan had yet another high-profile moment—this time an on-the-mound fight. After Ryan hit Robin Ventura of the Chicago White Sox with a pitch, Ventura charged the mound in order to fight Ryan, who was 20 years his senior. Ryan secured the 26-year-old Ventura in a headlock with his left arm, while pummeling Ventura's head with his right fist six times before catcher Iván Rodríguez was able to pull Ventura away from Ryan. Ryan stated afterwards it was the same maneuver he used on steers he had to brand on his Texas ranch. Videos of the incident were played that evening throughout the country. While Ventura was ejected, Ryan–who had barely moved from his spot on the mound in the fracas–was allowed to remain in the game. White Sox manager Gene Lamont vehemently argued this, leading to his own ejection. Ryan pitched a hitless ball game the rest of the way. He had been determined to be more aggressive after coming out on the wrong side of an altercation with Dave Winfield in 1980.
Ryan's arm gave out in Seattle on September 22, 1993, when he tore a ligament. The injury ended his career two starts earlier than planned, at age 46. Ryan briefly attempted to pitch past the injury, and he threw one additional pitch after tearing his ligament. With his injured arm, his final pitch was measured at 98 miles per hour (158 km/h). Ryan's last start was his career worst; he allowed a single, four walks, and a grand slam in the top of the first without recording an out. It was his record-setting 10th grand slam given up of his career. (Ryan left trailing 5–0, and the fourth walk was completed by a reliever after Ryan's injury, but credited to Ryan.) Greg Myers of the California Angels was the last strikeout victim of Nolan Ryan's career, on September 17, 1993.