Ortiz's towering shot to right-center against Carlos Carrasco had an exit velocity of 107.6 mph according to Statcast™ and traveled 398 feet.
It was a big hit, as it slimmed Cleveland's lead to 5-3. Hanley Ramirez followed with a homer to right. The Red Sox rallied for four runs in the inning to take the lead.
"When light goes on, so does Papi," Ortiz said after Tuesday's 6-2 win on Opening Day.
Gary Sheffield, who has 509 homers, is next in Ortiz's sights.
Murray, a switch-hitter, played for the Indians from 1994-96.