In early 2015, Bautista earned 10-and-5 rights by having at least 10 years of service time in the big-leagues, with the last 5 being on the same team.
These rights give Bautista the ability to veto any trade he would be involved in.
In a home game against the Orioles on April 21, Bautista hit his 250th career home run.
 He injured his right shoulder during that game, attempting to throw out Delmon Young at first base.
He was held out of the lineup for several days before returning, exclusively as the designated hitter.
Bautista received a cortisone shot on May 24 and returned to the outfield on June 2, against the Washington Nationals.
On July 6, Bautista was named to his sixth-consecutive All-Star team, as a reserve outfielder in Cincinnati.
However, on July 11 it was announced that he would sit out the game due to a shoulder injury.
Bautista tied Vernon Wells for second place on the Blue Jays' all-time home run list on July 21, when he hit his 223rd home run for Toronto in a 7–1 win over the Athletics.
He surpassed Wells on July 24 in a 5–2 loss to the Seattle Mariners.

On September 30, Bautista surpassed the 40 home run mark for the third time in his career, hitting a solo shot in the ninth inning against the Baltimore Orioles to extend the Blue Jays lead to 11–1.
The Blue Jays would win the game, 15–2, and clinch the American League East.

Bautista finished the 2015 regular season with a .250 batting average, 40 home runs, and 114 RBI.
He also walked more than he struck out for the second consecutive year, totaling 110 walks to 106 strikeouts.
For the season, he had the lowest line drive percentage of all major league hitters (13.9%).
From 2010–15, he batted .268 with 153 doubles, 227 home runs, 582 RBI, 574 walks, 576 strikeouts, .390 OBP, .555 SLG, .945 OPS, and 156 OPS+.
In that span, he hit more home runs than any other major leaguer – 28 ahead of second-place Miguel Cabrera – was second in slugging percentage and walks, third in OPS and OPS+ and fifth in OBP.

On October 8, 2015, with just over 1,400 career games played, Bautista made his postseason debut against the Texas Rangers in the American League Division Series (ALDS).
 In the fifth and final game of the series on October 14, Bautista hit a three-run home run off Sam Dyson that gave the Jays a 6–3 lead that they would not relinquish, sending Toronto to the American League Championship Series (ALCS).
 Bautista watched the home run and flipped his bat high into the air before running the bases, a celebratory gesture that was applauded by Jays fans and media outlets, while drawing the ire of Rangers players as unsportsmanlike, in the midst of a 53-minute seventh inning laden with controversy.
 A vital symbol of Toronto's first postseason appearance since 1993, the bat flip was voted Esurance's MLB Award for Best Play on Offense for 2015.
 In the five games of the ALDS, Bautista batted .273 with two home runs and five RBI.

In Game 3 of the ALCS against the Kansas City Royals, Bautista had one hit and two walks, joining Keith Hernandez as the only players in MLB postseason history to reach base three times on their birthday.
The Blue Jays would win the game, 11–8.
 In Game 6, Bautista hit two home runs, including a two-run game-tying homer at the top of the eighth inning to tie the game at 3–3; however Kansas City would win 4–3 to take the pennant.

On November 3, 2015, Toronto exercised Bautista's $14 million option for 2016.
In early 2015, Bautista earned 10-and-5 rights by having at least 10 years of service time in the big-leagues, with the last 5 being on the same team. These rights give Bautista the ability to veto any trade he would be involved in. In a home game against the Orioles on April 21, Bautista hit his 250th career home run.  He injured his right shoulder during that game, attempting to throw out Delmon Young at first base. He was held out of the lineup for several days before returning, exclusively as the designated hitter. Bautista received a cortisone shot on May 24 and returned to the outfield on June 2, against the Washington Nationals. On July 6, Bautista was named to his sixth-consecutive All-Star team, as a reserve outfielder in Cincinnati. However, on July 11 it was announced that he would sit out the game due to a shoulder injury. Bautista tied Vernon Wells for second place on the Blue Jays' all-time home run list on July 21, when he hit his 223rd home run for Toronto in a 7–1 win over the Athletics. He surpassed Wells on July 24 in a 5–2 loss to the Seattle Mariners.
On September 30, Bautista surpassed the 40 home run mark for the third time in his career, hitting a solo shot in the ninth inning against the Baltimore Orioles to extend the Blue Jays lead to 11–1. The Blue Jays would win the game, 15–2, and clinch the American League East.
Bautista finished the 2015 regular season with a .250 batting average, 40 home runs, and 114 RBI. He also walked more than he struck out for the second consecutive year, totaling 110 walks to 106 strikeouts. For the season, he had the lowest line drive percentage of all major league hitters (13.9%). From 2010–15, he batted .268 with 153 doubles, 227 home runs, 582 RBI, 574 walks, 576 strikeouts, .390 OBP, .555 SLG, .945 OPS, and 156 OPS+. In that span, he hit more home runs than any other major leaguer – 28 ahead of second-place Miguel Cabrera – was second in slugging percentage and walks, third in OPS and OPS+ and fifth in OBP.
On October 8, 2015, with just over 1,400 career games played, Bautista made his postseason debut against the Texas Rangers in the American League Division Series (ALDS).  In the fifth and final game of the series on October 14, Bautista hit a three-run home run off Sam Dyson that gave the Jays a 6–3 lead that they would not relinquish, sending Toronto to the American League Championship Series (ALCS).  Bautista watched the home run and flipped his bat high into the air before running the bases, a celebratory gesture that was applauded by Jays fans and media outlets, while drawing the ire of Rangers players as unsportsmanlike, in the midst of a 53-minute seventh inning laden with controversy.  A vital symbol of Toronto's first postseason appearance since 1993, the bat flip was voted Esurance's MLB Award for Best Play on Offense for 2015.  In the five games of the ALDS, Bautista batted .273 with two home runs and five RBI.
In Game 3 of the ALCS against the Kansas City Royals, Bautista had one hit and two walks, joining Keith Hernandez as the only players in MLB postseason history to reach base three times on their birthday. The Blue Jays would win the game, 11–8.  In Game 6, Bautista hit two home runs, including a two-run game-tying homer at the top of the eighth inning to tie the game at 3–3; however Kansas City would win 4–3 to take the pennant.
On November 3, 2015, Toronto exercised Bautista's $14 million option for 2016.
José Bautista