The Royals, leading the American League in hitting (.278) entering Friday, had 20 hits off six Boston pitchers, including utilityman Bill Hall, making his first big league appearance as a pitcher.
Kansas City had five straight singles to open the fourth, and with two out Betancourt lofted a knuckleball from Tim Wakefield into the seats above the Green Monster in left for the second grand slam of his career as the Royals beat Boston for the second straight night.
The Royals pummeled Wakefield (1-3) for 12 hits and nine runs in just 3 2-3 innings.
Mitch Maier had three hits for the Royals, including his first home run of the season.
Royals starter Kyle Davies (4-3) worked five shaky innings for his fourth win.
The Red Sox scored three times in the bottom of the first. Marco Scutaro doubled down the left field line and, with one out, David Ortiz took advantage of the shift and rolled an RBI single into left. After Kevin Youkilis walked, Victor Martinez, returning to the lineup for the first time since hurting his toe Monday, hit a two-run double to the 420-foot mark in right-center.
The 43-yer-old Wakefield, who returned to the rotation when Josh Beckett went down with a back injury on May 17 and beat the Phillies in his last start, wriggled out of a bases-loaded jam in the second by getting Scott Podsednik to fly out, but the Royals struck for two runs in the third.
Mike Aviles singled and rolled home on a double to left-center by David DeJesus. With one out, Jose Guillen walked and Sox third baseman Adrian Beltre, after getting one out, threw wide to first on what might have been an inning-ending double-play grounder by Alberto Callaspo. Maier followed with an RBI single.
After Youkilis walked again in the third, Martinez lined his seventh home run into the Royals' bullpen in right field to give the Red Sox a 5-2 lead.
Kyle Farnsworth and Dusty Hughes pitched four scoreless innings in relief of Davies for Kansas City.
NOTES: Royals are 9-5 since Ned Yost took over as manager. ... The Red Sox placed outfielder Jacoby Ellsbury on the 15-day disabled list Friday after he continued to complain of soreness and pain in the rib cage area. ... Red Sox manager Terry Francona said there was no timetable for Ellsbury's return. "We hope it's quick, but we don't know." The Red Sox recalled pitcher Scott Atchison from Pawtucket to take Ellsbury's place on the roster. ... The Royals' DeJesus extended his hitting streak to 10 games. ... Youkilis walked for the 30th and 31st time in May and reached base for the 27th straight game.
Victor Martinez returned to the lineup as a catcher for the first time since injuring his toe Monday Josh Beckett threw 22-25 pitches in a side session as he continues to recover from the back injury that put him on the disabled list. "we're going to be cautious with him," said Francona.