Mendoza gave up seven runs in all, as his ERA went from 1.80 in his first two starts to 9.00. The Rangers' rotation ERA also went up from 3.65 -- third best in the league -- to 4.18.
"I'm disappointed about tonight," Mendoza said. "I just have to think about the next start."
Mendoza had retired the first eight batters he faced before rookie shortstop Jed Lowrie, in his second start since being called up from the Minor Leagues, doubled down the left-field line to get the Red Sox started with two outs in the third.
"For the first two innings, I thought he really had something going," Rangers manager Ron Washington said. "All of a sudden, he lost the feel of his sinker and couldn't get it over."
Instead, Mendoza started leaving his sinker below the strike zone, and he couldn't get his other pitches over the plate. He walked both Ellsbury and Pedroia to load the bases to bring up Ortiz.
"Those two guys who ended up walking, if they get on base, you want them to hit their way on," Washington said. "That little second baseman is an aggressive hitter. You really have to do something to walk him."
The two walks prompted Rangers pitching coach Mark Connor to go to the mound with a message on how to pitch to Ortiz.
Connor said he told Mendoza: "This guy is going to be aggressive; he wants to swing the bat. Try to get him to swing at something down and out of the zone."
Mendoza apparently didn't heed the message.
"I just tried to stay ahead with the first pitch," Mendoza said. "The two walks I was behind in the count, so I tried to start ahead and left a ball in the middle of the plate."
The grand slam was both Ortiz's second home run and extra-base hit of the season. His other was a home run against the Athletics on April 2. He had gone 12 games since then without an extra-base hit, and he was hitting just .111 on the season before Friday's game.
"Even when the big boy is struggling, he's still dangerous," Washington said.
The Rangers had given Mendoza a 1-0 lead against Red Sox starter Daisuke Matsuzaka in the third, when Ian Kinsler doubled with one out, stole third and scored on a Josh Hamilton sacrifice fly.
But Mendoza couldn't build on his strong start, and the Rangers have lost 33 of their past 45 games at Fenway Park.
"He went through the first eight hitters like Grant through Richmond," Connor said. "It was good, but then you had a bloop double and the wheels came off. He's always relied on his sinking fastball, but there's going to come a point in time up here where he's going to have to use his offspeed stuff and slow people down.
"He's got a great future. He's not scared one bit. He just tried to be too fine in that one inning and tried too hard to get that third out."
Mendoza managed to get out of the third inning, but he ran into more trouble in the fourth. He walked J.D. Drew, and Jason Varitek followed with an RBI double. Sean Casey singled him to third and Mendoza was done.
Reliever Josh Rupe took over, but the Red Sox's blitz continued. Lowrie hit a sacrifice fly to score one run, and Ellsbury tripled to center to make it 7-1. Then Pedroia went deep to left, and the Red Sox were sitting on a 9-1 lead.
"After the grand slam, I still felt good," Washington said. "I thought if we could hold them, we could get one run here, one run there and get back in it. We made Daisuke work. He was the recipient of a lot of runs, because I don't think he pitched that well. But they scored those five runs."
Rupe ended up pitching four innings in relief, and he could be sent down when closer Eddie Guardado is activated off the disabled list on Sunday. Mendoza will get back on the hill on Wednesday against the Tigers.