Cashner, who learned late Sunday night he was being promoted from Triple-A Iowa, arrived in Pittsburgh in time to retire Ronny Cedeno on a popup in the eighth inning of the Pirates' 2-1 victory on Monday.
Cashner moved into the Cubs' bullpen in place of left-hander John Grabow, who went on the disabled list with left knee inflammation.
The right-handed Cashner was a starter in the Cubs' farm system until moving to the bullpen last week. The 23-year-old was 3-0 at Iowa with a 0.86 ERA in five games, including three starts.
"Nothing makes it any easier, but definitely the nerves will be down [the next time]," Cashner said of pitching in a major league game. "I was a little nervous out there. But I was able to control my emotions and make a pitch."
Cashner called it "a real big moment," and his parents were able to watch it after hastily catching a flight to Pittsburgh.
Cashner, the Cubs' first-round pick in 2008, started the season by going 3-1 with a 2.75 ERA in six starts at Double-A Tennessee.
"He's got electric stuff," Cubs starter Randy Wells said of the former TCU pitcher. "Hopefully he takes off and becomes a superstar."
For now, Cashner is expected to be used in the sixth or seventh innings, but he could move into a setup role soon.
"Yeah, he had a good debut," manager Lou Piniella said. "He threw a good fastball to get Cedeno out. He'll help us. He has a nice arm."
Grabow is expected to rest for several days before beginning to work himself back into game shape. He is 0-3 with a 9.45 ERA, giving up a pair of home runs in the ninth inning of a 9-1 loss to St. Louis on Sunday.