在《生化危機5》中為阿爾伯特·威斯克提供配音的演員Ken Lally表示會在《使命召喚：現代戰爭2》中提供配音，但尚未表明配音的角色。歌手50 Cent也會為特種部隊模式和多人遊戲模式進行團隊指揮官語音的配音。除了名人，一些參與《使命召喚4：現代戰爭》的配音演員也會參與《使命召喚：現代戰爭2》相同角色的配音工作。著名電影配樂人漢斯·季默則是遊戲音樂創作的總負責人。
遊戲上市不久，官方即發布了遊戲音樂原聲專輯（Original Soundtrack）。
專輯曲目如下：
01 - Opening Titles (2.19)
02 - Opening Credits (3.14)
03 - Main Menu (1.52)
04 - Spec Ops Menu (3.01)
05 - Same Shit, Different Day (8.18)
06 - Cliffhanger (1.37)
07 - Infiltration (2.44)
08 - The Satellite - Comprimised (2.45)
09 - Plan B (2.12)
10 - snowmobile Chase (4.41)
11 - 'Remember...No Russian' (5.30)
12 - Takedown (6.39)
13 - Chasing Rojas (5.42)
14 - Ranger's Lead the Way (5.07)
15 - The Hornet's Nest (4.14)
16 - Waveoff (1.30)
17 - Roach's Fall - Final Run - Escape (2.03)
18 - Exodus (3.09)
19 - Panicroom (1.11)
20 - The Only Easy Day...Was Yesterday Part 1 (5.12)
21 - The Only Easy Day...Was Yesterday Part 2 (3.28)
22 - The Only Easy Day...Was Yesterday Part 3 (4.44)
23 - TF-141 Assaults the Gulag (6.11)
24 - The Armory - Searching the Cells (5.43)
25 - To the Shower Room - Prisoner #627 (6.52)
26 - Extraction from the Gulag (2.16)
27 - D.C. Burning (3.51)
28 - Of their Own Accord - Crow's Nest (5.33)
29 - Evacuation - Crash Site (2.31)
30 - Contingency (11.21)
31 - Assaulting the Submarine Base - Launch (5.45)
32 - ISS (4.16)
33 - Second Sun (3.11)
34 - The President's Bunker (2.19)
35 - Whiskey Hotel - Green Flares (7.51)
36 - Makarov's Safehouse (5.26)
37 - Breaching & Clearing (3.44)
38 - Escape from the Safehouse - Loose Ends (4.09)
39 - The Enemy of My Enemy is My Friend (8.27)
40 - Just Like Old Times (2.46)
41 - Infiltrating Site Hotel Bravo (4.24)
42 - Going Loud - The Control Room (6.55)
43 - Zodiac Chase & Waterfall - Endgame (4.31)
44 - End Credits (3.23)
