"That was my one thing. Mookie had to take that from me, too," Holt said after the game, according to MLB.com's Ian Browne.
The 25-year-old Betts, who announced on Wednesday that he and his partner are expecting a baby, led off the game in the top of the first with a single to left field.
In the second inning, Betts collected the most difficult hit of any cycle by knocking a triple, also to left field. Continuing to pepper left field, Betts dropped a double in his fourth-inning at-bat.
After going 3-for-3, Betts took an anti-climactic walk in the sixth frame before hitting his 27th home run of the year in the ninth. The Red Sox superstar reached base in all five of his plate appearances.
Including Thursday's dominant showing, Betts now owns a remarkable .347/.434/.668 slash line. His 192 wRC+ jumps ahead of Mike Trout for the league lead.