And Travis Shaw, who figures to lose playing time to Moncada at third base, merely hit a homer and two doubles. Shaw produced his fourth five-RBI game this season.
Moncada, a 21-year-old who was ranked No. 5 in ESPN Insider Keith Law's midseason top 50 prospects list, entered the game as a defensive replacement in the seventh inning.
Wearing No. 65, the Cuban made a nice play on his first chance at third base, fielding Chad Pinder's grounder near the line and the outfield grass, and making a strong throw to first for the final out of the inning.
In the top of the eighth, Moncada drew a five-pitch walk in his first major-league plate appearance. He then motored home on Shaw's second double.
Through interpreter Daveson Perez, Moncada discussed his initial taste of the big leagues.
"It was a culture shock," he said. "You see the big stadium. You're a little nervous before the game. The nerves are there, but it felt good to be out there. Looking forward to the future."
Said manager John Farrell: "In a three-inning look, you see some exciting skills." Farrell mentioned Moncada's throw on Pinder's grounder and what he called the "outstanding" speed Moncada displayed scoring on Shaw's double.
"It was a glimpse," Farrell said, "but he had a chance to show off two of the tools."
Moncada struck out swinging against Chris Smith in the ninth. As impressive as Moncada's numbers were with Class A Salem and Double-A Portland this season -- a combined .294 with 31 doubles, 6 triples, 15 homers and 45 stolen bases -- he did have some trouble making contact. Moncada struck out 64 times in 207 plate appearances with Portland.
Farrell said Moncada, a switch-hitter who has had more success batting left-handed, will start at third base Saturday night and will get the bulk of the starts against right-handed pitching.
Farrell said Aaron Hill will start at third when the Red Sox face lefties. Hill also could be a late-inning defensive replacement for Moncada.
Only a few minutes after the A's honored Ortiz with a video tribute and a large bottle of cabernet, he put the Red Sox in front. In the first inning, Ortiz ripped an Andrew Triggs pitch to right-center to bring home Xander Bogaerts from second for a 1-0 lead.
The Coliseum has not been a particularly good park for Ortiz; coming into Friday's game, he had a .219 career average (49-for-224) in Oakland.
Triggs departed after one inning because of back tightness. Fellow right-hander Zach Neal (2-4) replaced him.
It was a 2-2 game in the fifth before five consecutive two-out hits led to four Boston runs.
After Bogaerts lined a double to left, Ortiz brought him home with a solid single just to the left of second base. The Red Sox were ahead to stay.
Boston put away the game with six runs in the sixth. Ortiz had a sacrifice fly in the inning and Shaw capped the rally with a three-run homer to right, his 15th of the season.
Meanwhile, David Price (14-8) gave up two runs and four hits in seven innings. In 2008, Price was in a similar situation to what Moncada is experiencing now.
Price was 23, had been the first pick of the draft by Tampa Bay a year earlier and made his big-league debut in September in the middle of a pennant race.
He said he'd give Moncada the same advice Philadelphia pitcher Jamie Moyer, then 46, gave to Price before the Phillies faced Tampa Bay in the World Series.
Price said Moyer told him, "Have fun. Enjoy it. It goes by really fast." Price added, "That really kind of took me back right there. ... It really stuck with me. You've got to have fun with it."
The Red Sox moved one game back of the Toronto Blue Jays for first place in the AL East. The Red Sox remained two games in front of Baltimore and Detroit at the top of the AL wild-card standings.
The Red Sox are 4-0 against Oakland this season and have scored at least 13 runs in each of the four games.