According to second baseman Brian Dozier, Hamels has thrived when getting hitters to chase pitches outside the zone, particularly with his cutter. So the Twins' approach to attacking the tough lefty was to focus on being patient and force Hamels into mistakes while in hitters' counts.
Fortunately for the Twins, Hamels couldn't find his fastball command, and they were able to take advantage.
"He lives off his cutter to the changeup," Dozier said. "He wasn't really commanding that cutter. [Miguel] Sano made him throw it every time to him, and he kept taking some really good pitches right off the plate, and then he had to go to his fastball and he lost command and started leaving stuff right over the middle of the plate.
"Against good pitchers like that, you really have to take advantage of their mistakes, and we did that today."
Dozier pointed to his two-run triple in the third inning as a good example of the Twins' approach.
In his first at-bat, Dozier struck out swinging on two straight changeups that dropped out of the bottom of the strike zone, and as he expected, Hamels attacked him with two changeups again in his second at-bat -- but this time, Dozier was taking.
After that, Hamels was forced to attack the zone to get back into the count. He missed his spot with a fastball and left it right down the middle. Dozier didn't miss, driving it off the wall in right-center to give the Twins the lead.
Robbie Grossman's ensuing RBI single was more of the same: He took the first two pitches for balls and got a 2-0 fastball in the heart of the strike zone that he drove right up the middle for a hit.
As further evidence of the Twins' patient approach, noted free-swinger Sano didn't swing on a single cutter he saw and only once swung and missed on a Hamels pitch -- a changeup in the fifth. He took the next two pitches for a walk that set up a two-run rally to chase Hamels.
Max Kepler, who set a Twins rookie record with seven RBIs in Saturday's win, drove in a fifth-inning run with a single, which brought Hamels' day to an end.
Hamels had been 4-0 with a 1.04 ERA in his last five starts and had won his last nine decisions on the road dating back to 2015, setting a new Rangers record. His 2.60 ERA in 2016 and his 1.44 road ERA were both third in the American League entering Sunday.
But against the Twins and their approach, he set season lows with four-plus innings pitched and three strikeouts while yielding a season-high five earned runs and 10 hits.
"Hamels was having a great year -- we just found a way to square some balls up," Twins manager Paul Molitor said.
Do-Hyoung Park is a reporter for MLB.com based in Minneapolis.