| 48 || May 24 || Tigers || 0–1 || Knotts (2–3) || Loaiza (7–2) || Germán (1) || 2:35 || 27,535 || 22–26 || box |- style="text-align:center;background-color:#bbffbb" | 49 || May 25 || Tigers || 8 – 5 (12) || Glover (1–0) || Sparks (0–1) || || 3:32 || 21,398 || 23–26 || box |- style="text-align:center;background-color:#ffbbbb" | 50 || May 26 || @ Blue Jays || 5–11 || Towers (1–0) || Buehrle (2–8) || Tam (1) || 3:16 || 19,009 || 23–27 || box |- style="text-align:center;background-color:#ffbbbb" | 51 || May 27 || @ Blue Jays || 1–5 || Halladay (6–2) || Colón (5–4) || || 2:18 || 19,365 || 23–28 || box |- style="text-align:center;background-color:#bbffbb" | 52 || May 28 || @ Blue Jays || 8–0 || Garland (3–4) || Escobar (2–2) || || 2:48 || 36,806 || 24–28 || box |- style="text-align:center;background-color:#bbffbb" | 53 || May 29 || @ Blue Jays || 3–2 || Loaiza (8–2) || Lidle (8–3) || Koch (6) || 2:54 || 20,010 || 25–28 || box |- style="text-align:center;background-color:#ffbbbb" | 54 || May 30 || @ Indians || 3–7 || Sabathia (4–2) || Wright (0–3) || || 2:57 || 24,666 || 25–29 || box |- style="text-align:center;background-color:#bbbbbb" | – || May 31 || @ Indians ||colspan=8| Postponed (rain), rescheduled for July 12 |- style="text-align:center;background-color:#ffbbbb" | 55 || June 1 || @ Indians || 4 – 5 (10) || Boyd (1–1) || Koch (1–2) || || 2:54 || 22,681 || 25–30 || box |- style="text-align:center;background-color:#ffbbbb" | 56 || June 2 || @ Indians || 2–5 || Anderson (3–5) || Colón (5–5) || Báez (11) || 2:40 || 20,892 || 25–31 || box |- style="text-align:center;background-color:#ffbbbb" | 57 || June 3 || @ D-backs || 1–2 || Villarreal (4–3) || Gordon (2–5) || || 2:33 || 33,544 || 25–32 || box |- style="text-align:center;background-color:#ffbbbb" | 58 || June 4 || @ D-backs || 6–8 || Good (2–1) || Garland (3–5) || Valverde (1) || 2:43 || 26,667 || 25–33 || box |- style="text-align:center;background-color:#bbffbb" | 59 || June 5 || @ D-backs || 3 – 2 (10) || Koch (2–2) || Service (0–2) || || 2:50 || 27,747 || 26–33 || box |- style="text-align:center;background-color:#ffbbbb" | 60 || June 6 || @ Dodgers || 1–2 || Ishii (5–2) || Buehrle (2–9) || Gagné (21) || 2:20 || 35,503 || 26–34 || box |- style="text-align:center;background-color:#bbffbb" | 61 || June 7 || @ Dodgers ||