The Red Sox will also get their first look at Yankees pitching phenom Masahiro Tanaka in Tuesday night's opener to a three-game series.
Ellsbury spent his first seven seasons with the Red Sox, who drafted him 23rd overall in 2005. His best performance came in 2011, when he became the only Boston player with at least 30 home runs and 30 stolen bases and finished second in the AL MVP voting. After helping Boston win the 2013 World Series, the outfielder signed a seven-year, $153 million deal with the Yankees in December.
"I always enjoyed playing there," Ellsbury told the Yankees' website. "I still have a lot of friends over there. I'm looking forward to it. I'll have some family there (at Fenway), as well."
Ellsbury is hitting .338 for his new club and was 5 for 14 against his former team as New York took three of four from Boston in the Bronx from April 10-13.
The Yankees (11-8) are back home after a 5-1, 12-inning victory at Tampa Bay on Sunday to split a four-game set.
Tanaka (2-0, 2.05 ERA) struck out 10 for the second straight game Wednesday in a 2-0 victory over the Chicago Cubs. The right-hander gave up two bunt singles - including one awarded after a replay - and one walk over eight innings.
Tanaka has 28 strikeouts and two walks in his first three starts. The strikeouts are the most by a Yankees pitcher in his first three career starts, and Stephen Strasburg's 41 strikeouts in 2010 are the most by any pitcher in his first four MLB starts since at least 1914.
"I'm sure that the fans will be heated up a bit," Tanaka said through an interpreter. "I've seen the two teams play (on TV), and I understand there's a rivalry between the two teams going into the game. It should be a good experience going up on the mound that day and I'm very much looking forward to it."
Tanaka will face a Red Sox team that's hitting .238 and has one of the AL's worst slugging percentages at .361. Boston (9-11), however, produced 20 runs in its four-game series against Baltimore and 11 hits in two contests.
The Red Sox had to settle for a split after its comeback from a six-run deficit fell short in a 7-6 loss on Patriots' Day and the first running of the Boston Marathon since last year's bombing.
"Special day. ... Of course, we wanted to go out there and win," first baseman Mike Napoli told the team's website. "We fought hard, but it fell short. But we've got a big series (vs. the Yankees) coming up. We'll take it one day at a time and try to get on track."
Scheduled starter Jon Lester (2-2, 2.17) gave up one run over eight innings while fanning a season-high nine in a 3-1 win over the Chicago White Sox on Thursday. In his prior outing, he yielded two runs over 6 2-3 innings in a 4-2 victory at Yankee Stadium. The Red Sox dropped the next two games in that series but won six of nine matchups at Fenway in 2013.
Derek Jeter, riding a 10-game hit streak, is 22 for 66 all-time against Lester. Ichiro Suzuki has 11 singles in his last 26 at-bats versus the left-hander.