|| W1 |- |- bgcolor="#ffbbbb" | 2 || April 2 || @ Angels || 5–7 || Weber (1–0) || Riske (0–1) || Percival (1) || Edison International Field of Anaheim || 20,055 || 1–1 || L1 |- bgcolor="#bbffbb" | 3 || April 3 || @ Angels || 6–5 || Drese (1–0) || Sele (0–1) || Wickman (1) || Edison International Field of Anaheim || 18,194 || 2–1 || W1 |- bgcolor="#ffbbbb" | 26 || April 30 || Angels || 2–21 || Ortiz (2–3) || Sabathia (2–3) || || Jacobs Field || 24,286 || 13–13 || L3 |- |- bgcolor="#ffbbbb" | 27 || May 1 || Angels || 2–7 || Washburn (3–2) || Drese (2–3) || || Jacobs Field || 23,536 || 13–14 || L4 |- bgcolor="#ffbbbb" | 28 || May 2 || Angels || 0–8 || Appier (3–1) || Finley (2–3) || || Jacobs Field || 26,068 || 13–15 || L5 |- |- bgcolor="#bbffbb" | 78 || June 28 || Diamondbacks || 8–2 || Sabathia (6–6) || Batista (4–5) || || Jacobs Field || 42,586 || 37–41 || W1 |- bgcolor="#ffbbbb" | 79 || June 29 || Diamondbacks || 2–4 || Anderson (3–7) || Finley (4–10) || Kim (20) || Jacobs Field || 42,466 || 37–42 || L1 |- bgcolor="#ffbbbb" | 80 || June 30 || Diamondbacks || 2–5 || Schilling (13–3) || Báez (6–6) || || Jacobs Field || 42,221 || 37–43 || L2 |- |- bgcolor="#ffbbbb" | 120 || August 16 || @ Angels || 4–5 || Lackey (5–2) || Drese (9–9) || Percival (29) || Edison International Field of Anaheim || 41,356 || 53–67 || L2 |- bgcolor="#bbffbb" | 121 || August 17 || @ Angels || 9–4 || Sadler (1–0) || Washburn (15–4) || || Edison International Field of Anaheim || 39,866 || 54–67 || W1 |- bgcolor="#ffbbbb" | 122 || August 18 || @ Angels || 1–4 || Appier (11–9) || Sabathia (8–10) || Percival (30) || Edison International Field of Anaheim || 41,059 || 54–68 || L1 |- |- style="text-align:center;" | Legend: = Win = Loss = PostponementBold = Indians team member |-align="center" bgcolor="#bbffbb" | 1 || March 31 || @ Angels || 6–0 || Colón (1–0) || Washburn (0–1) || || 42,697 || 1–0 |- |-align="center" bgcolor="ffbbbb" | 2 || April 2 || @ Angels || 7–5 || Weber (1–0) || Riske (0–1) || Percival (1) || 20,055 || 1–1 |-align="center" bgcolor="#bbffbb" |