[28] March 29–March 31, at Tampa Bay Rays After the tough loss on opening day, David Price made his 2018 debut and threw seven shut-out innings on just 76 pitches.

Boston again jumped out to an early lead in the second game; up 6–0 after three, starter Rick Porcello and the bullpen held Los Angeles scoreless, for a 9–0 victory.

In the bottom of the 10th inning, Curtis Granderson hit a one-out solo home run off of Craig Kimbrel to give the Blue Jays a 4–3 win, extending Boston's losing streak to three games.

[37] In the fourth and final game of the series, Chris Sale held the Rangers to four hits and one run in seven innings of work, en route to a 6–1 Red Sox victory.

Kelly then held the Yankees scoreless in the bottom of the eighth, and Craig Kimbrel pitched a one-two-three ninth, earning his tenth save of the season.

In the second game of the series, David Price pitched 5+1⁄3 innings, giving up two runs and getting the win, after his scheduled start against the Yankees had been pushed back due to numbness in his throwing hand, which was subsequently diagnosed as a mild case of carpal tunnel syndrome.

After starter Drew Pomeranz left with no outs in the fifth inning, the Red Sox bullpen allowed one inherited runner to score, and then held Toronto to no further runs through the end of the game.

In the final game of the series, a pair of J. D. Martinez home runs helped lead Boston to a 5–0 win; the Orioles outhit the Red Sox, 13–12, but were unable to score as they had 14 men left on base.

The second game of the series also yielded an 8–3 Boston win, as the Red Sox scored in six of the eight innings they batted, including home runs from Benintendi and Sandy León.

A two-run Andrew Benintendi homer provided the winning edge, while Dustin Pedroia was placed on the 10-day disabled list after appearing in only three games since making his season debut on May 26.

Steven Wright, starter of the third game of the series, held Seattle to one run through seven innings, but Boston was limited to two hits and unable to score, as the Red Sox fell 1–0 to the Mariners.

The two teams used a combined 12 pitchers, with Angels reliever Jake Jewell leaving the game after an apparent ankle injury suffered while trying to make a play at the plate.

In the second game of the series, the Red Sox had a pair of three-run home runs from Eduardo Núñez and Xander Bogaerts, plus a two-run shot from J. D. Martinez, en route to an 11–4 win.

The third game of the series went to extra innings, after Boston scored the tying run in the bottom of the ninth on back-to-back doubles by Xander Bogaerts and Jackie Bradley Jr.

Recently acquired starting pitcher Nathan Eovaldi made his Red Sox debut, allowing four hits in seven innings while striking out five and issuing no walks.

Ian Kinsler had to leave the game due to injury, and was later placed on the disabled list; Betts replaced him at second base for several innings, his first time playing the position since 2014.

A Bogaerts grounder then drew an errant throw from Yankees third baseman Miguel Andújar, allowing Jackie Bradley Jr. to score the tying run.

In the second game of the series, Cleveland collected 13 hits en route to a 6–3 win, giving Boston their third consecutive loss for only the second time during the season, the first being in April.

The Red Sox then won the game in the bottom of the ninth when the Marlins were unable to turn a double play on an Eduardo Núñez ground ball, allowing J. D. Martinez to score on a throwing error.

Chris Sale returned from the disabled list, pitching the first inning as the Red Sox used seven pitchers in relief, with Ryan Brasier getting the win.

Brock Holt hit a three-run pinch-hit home run, as the Red Sox became the first major league team to clinch a spot in the 2018 postseason.

David Price got the win for Boston, while J. D. Martinez, Xander Bogaerts, and Blake Swihart each had home runs and Rafael Devers went 4-for-5 including two homers and six RBIs.

In addition, Brock Holt hit for the cycle, the first player ever to do so in an MLB postseason game, capping off his performance with a ninth-inning home run against catcher Austin Romine, brought in to pitch when the New York bullpen was overtaxed.

Game 1 was highlighted by neither Chris Sale nor Clayton Kershaw making it through the fifth inning, and a pinch hit three-run home run by Eduardo Núñez, as Boston won, 8–4.

Game 2 starter David Price held the Dodgers to two runs on three hits in six innings, while striking out five, picking up his second win of the postseason, as the Red Sox won, 4–2.

Nathan Eovaldi pitched six innings in relief, allowing only two hits prior to a walk-off home run by Max Muncy for a 3–2 Dodgers win.

The Red Sox stormed back with help from Mitch Moreland and Steve Pearce, scoring nine runs in the final three innings, winning the game, 9–6, for a 3–1 series lead.

† Minimum 3.1 plate appearances per team games played AVG qualified batters: Benintendi, Betts, Bogaerts, Bradley, Martinez, Nuñez

‡ Minimum 1 inning pitched per team games played ERA & WHIP qualified pitchers: Porcello, Price Infielders Coaches Red Sox players who made their MLB debuts during the 2018 regular season: Notable transactions of/for players on the 40-man roster during the 2018 regular season: Boston's first 15 selections in the 2018 MLB draft, held on June 4–6, are listed below.

[202] On September 15, 2017, commissioner Rob Manfred had said in regards to the investigation into Boston's illicit use of an Apple Watch: "I have received absolute assurances from the Red Sox that there will be no future violations of this type.