McDonald (6-3) allowed only one run in his previous appearance but still lost to Cleveland when the Pirates could not manage a single score.
Against the Twins, however, the Pirates pounded out 12 hits and made things easy for McDonald, as he cruised to his milestone achievement. He gave up six hits, struck out five and did not walk a batter.
Pittsburgh had built a 4-0 lead before the Twins scored their lone run in the fourth, and the Pirates then added three homers to turn the game into a runaway.
The Pirates won twice in the three-game interleague series and have captured four out of five.
Liam Hendriks (0-4) took the loss, surrendering three earned runs on eight hits over five innings. Hendriks is still looking for his first career victory, having made 10 starts scattered over two seasons with the Twins.