There are 28 starring cast members with a large supporting cast. The majority of the characters were drawn from the Second Platoon of the First Reconnaissance Battalion's Bravo Company. Lee Tergesen played embedded reporter Evan Wright, though throughout the series he is only referred to as "reporter" or "Rolling Stone". Wright was assigned to the lead vehicle of Bravo Company, which he shared with Staff Sergeant Brad "Iceman" Colbert, played by Alexander Skarsgård, Corporal Josh Ray Person, played by James Ransone and Lance Corporal Harold James Trombley, played by Billy Lush. To prepare for their roles as Recon Marines, the cast attended a six-day boot camp led by Eric Kocher and Rudy Reyes.

Other starring characters, from 2nd platoon include:
• Stark Sands as First lieutenant Nathaniel Fick
• Marc Menchaca as Gunnery Sergeant Mike "Gunny" Wynn
• Jon Huertas as Sergeant Antonio "Poke" Espera
• Mike Figueroa as Sergeant Leandro "Shady B" Baptista
• Josh Barrett as Sergeant Larry Shawn "Pappy" Patrick
• Sergeant Rodolfo "Rudy" Reyes as himself
• Jonah Lotan as Hospital Corpsman Second Class Robert Timothy "Doc" Bryan
• Wilson Bethel as Corporal Evan "Q-Tip" Stafford
• Pawel Szajda as Corporal Walt Hasser
• Rey Valentin as Corporal Gabriel "Gabe" Garza
• Sean Brosnan as Corporal Daniel Redman
• Kellan Lutz as Corporal Jason Lilley
• Rich McDonald as Corporal Anthony "Manimal" Jacks
• Eric Ladin as Corporal James Chaffin
• Daniel Fox as Private First Class John Christeson
Additional characters:
• Robert John Burke as Major general James "Chaos" Mattis, commanding officer of 1st Marine Division
• Chance Kelly as Lieutenant colonel Stephen "Godfather" Ferrando, commanding officer of the First Reconnaissance Battalion
• Benjamin Busch as Major Todd Eckloff, executive officer of the battalion
• Michael Kelly as Captain Bryan Patterson, commanding officer of Alpha Company
• Brian Patrick Wade as Captain Craig "Encino Man" Schwetje, commanding officer of Bravo Company
• Eric Nenninger as Captain Dave "Captain America" McGraw, the erratic commanding officer of 3rd platoon, Bravo company

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Although the series has no score, it features a large collection of music, much of it songs that were popular among the American populace in late 2002 and early 2003. The newer music (in the show's context) serves to illustrate pop culture during the time of the invasion. All of the songs are sung a cappella by cast members, with the exception of Johnny Cash's "The Man Comes Around" and Josh Ray Person's "Re-Up Time".

The miniseries received very positive reviews from critics. On Metacritic, it received a score of 80 out of 100 based on 27 reviews, indicating "generally favorable reviews". On Rotten Tomatoes, the miniseries has an approval rating of 86% based on 42 reviews, with an average rating of 9.1/10. The critical consensus reads, "Generation Kill plunges the viewer into war with a visceral force that's still somehow reined in by masterful storytelling and a strong command of period details." A red carpet screening of Generation Kill was held for U.S. Marines at Camp Pendleton in California, where the series was favorably received.

Entertainment Weekly gave the series an "A−" rating, and critic Ken Tucker remarked favorably on its avoidance of cliché, self-consciousness, and agenda-driven storytelling, and praised its execution, nuance, and verisimilitude. Robert Bianco of USA Today wrote: "the seven-part Generation Kill is what you'd hope for from the people behind The Wire: an honest, barely adorned, sometimes painfully vivid representation of life as we live it now. It's journalism converted to art, with both benefiting". Nev Pierce of Empire gave the miniseries a perfect five out of five stars. Brian Lowry of Variety says "HBO nails the target with Generation Kill". Tim Goodman of SFGate praised the series' authenticity and attention to detail. Writing for The New York Times, Alessandra Stanley remarked "Generation Kill has a superb cast and script, provides a searingly intense, clear-eyed look at the first stage of the war, and it is often gripping". Noel Murray of The A.V. Club wrote: "By the time Generation Kill's final chapter ends, Wright and company have created not just a nuanced, necessary explication of recent events, but an epic that can stand alongside the greatest long-form movies ever made". Pattie Pegler of Stuff said, "This is a complex, unwieldy tale that draws you in and isn't afraid to take its time. And, in that way it reminds me of The Wire – a brilliant piece of television that left you thinking long after you switched off. Generation Kill promises to be equally unforgettable."

Conversely, Austin Smith of the New York Post was not as impressed. He described the series "as dull and throbbing as a severe headache". Similarly, Troy Patterson of Slate wrote: "Generation Kill is too skeptical about authority to entertain neocons or red-meat nationalists and too depressing to delight a good liberal. It plays like it's been built for antisocial boys—armchair heroes in love with guns and in search of demented adventure."