3 || April 3 || @ Angels || 6–5 || Drese (1–0) || Sele (0–1) || Wickman (1) || 18,194 || 2–1 |-align="center" bgcolor="#bbffbb" | 4 || April 5 || @ Tigers || 10–1 || Báez (1–0) || Redman (0–1) || || 41,248 || 3–1 |-align="center" bgcolor="#bbffbb" | 5 || April 6 || @ Tigers || 5–3 || Colón (2–0) || Cornejo (0–1) || Wickman (2) || 19,754 || 4–1 |-align="center" bgcolor="#bbffbb" | 6 || April 7 || @ Tigers || 5–1 || Sabathia (1–0) || Weaver (0–1) || Wickman (3) || 14,749 || 5–1 |-align="center" bgcolor="#bbffbb" | 7 || April 8 || Twins || 9–5 || Drese (2–0) || Milton (1–1) || || 42,441 || 6–1 |-align="center" bgcolor="#bbffbb" | 8 || April 9 || Twins || 5–4 || Finley (1–0) || Mays (0–2) || Wickman (4) || 23,760 || 7–1 |-align="center" bgcolor="#bbffbb" | 9 || April 10 || Twins || 9–3 || Báez (2–0) || Reed (1–1) || || 25,420 || 8–1 |-align="center" bgcolor="#bbffbb" | 10 || April 11 || Twins || 8–4 || Colón (3–0) || Lohse (0–1) || || 25,582 || 9–1 |-align="center" bgcolor="#bbffbb" | 11 || April 12 || Royals || 3–1 || Sabathia (2–0) || Suppan (1–1) || Wickman (5) || 29,970 || 10–1 |-align="center" bgcolor="#bbffbb" | 12 || April 13 || Royals || 8–7 || Shuey (1–0) || Bailey (0–2) || || 28,455 || 11–1 |-align="center" bgcolor="#bbbbbb" | -- || April 14 || Royals || colspan=6|Postponed (rain) |-align="center" bgcolor="ffbbbb" | 13 || April 16 || @ White Sox || 10–5 || Marte (1–0) || Finley (1–1) || || 23,502 || 11–2 |-align="center" bgcolor="ffbbbb" | 14 || April 17 || @ White Sox || 7–2 || Buehrle (4–0) || Báez (2–1) || || 15,561 || 11–3 |-align="center" bgcolor="ffbbbb" | 15 || April 18 || @ White Sox || 7–1 || Ritchie (1–1) || Colón (3–1) || || 13,880 || 11–4 |-align="center" bgcolor="ffbbbb" | 16 || April 19 || @ Twins || 12–3 || Lohse (1–1) || Sabathia (2–1) || || 23,491 || 11–5 |-align="center" bgcolor="ffbbbb" | 17 || April 20 || @ Twins || 6–2 || Kinney (1–0) || Drese (2–1) || || 30,146 || 11–6 |-align="center" bgcolor="ffbbbb" | 18 || April 21 || @ Twins || 4–2 || Reed (2–1) || Finley (1–2) || Guardado (8) || 22,264 || 11–7 |-align="center" bgcolor="#bbffbb" | 19 || April 22 || White Sox || 4–2 || Báez