Part One is titled The Argentine and focuses on the Cuban Revolution from the landing of Fidel Castro, Guevara, and other revolutionaries in Cuba to their successful toppling of Fulgencio Batista's dictatorship two years later.

It stars Benicio del Toro as Guevara, with an ensemble cast that includes Demián Bichir, Rodrigo Santoro, Santiago Cabrera, Franka Potente, Julia Ormond, Vladimir Cruz, Marc-André Grondin, Lou Diamond Phillips, Joaquim de Almeida, Édgar Ramírez, Yul Vazquez, Unax Ugalde, Alfredo De Quesada, Jordi Mollá, Matt Damon, and Oscar Isaac.

There is a return to 1964 for Guevara's address before the United Nations General Assembly in New York City, where he makes an impassioned speech against American imperialism, and defends the executions his regime has committed, declaring "this is a battle to the death."

The Battle of Santa Clara is depicted with Guevara demonstrating his tactical skill as the guerrillas engage in street-to-street fighting and derail a train carrying Cuban soldiers and armaments.

The second part begins on 3 November 1966 with Guevara arriving in La Paz, Bolivia disguised as a middle-aged representative of the Organization of American States hailing from Uruguay, who subsequently drives into the mountains to meet his men.

By Day 113, some of the guerrillas have deserted, and, upon capture, have led the Bolivian Army to the revolutionaries' base camp, which contained vast stockpiles of food, much-needed supplies, and intelligence identifying much of the group as Cubans.

The next day, a helicopter lands and Cuban American CIA agent Alejandro Ramírez (a fictionalized version of Félix Rodríguez) emerges to interrogate Che, but without success.

[8] Del Toro and Bickford hired screenwriter Benjamin A. van der Veen to write the screenplay's first drafts, and their extensive research took them to Cuba where they met with several of the remaining members of Guevara's team in Bolivia as well as the revolutionary's wife and children.

In filming the sequence, Soderbergh balked at the digital effects solution and managed to reallocate $500,000 from the overall $58 million budget to build a real set of tracks and a train powered by two V-8 car engines.

"[22] According to Edgar Ramirez, who portrays Ciro Redondo, the cast "were improvising a lot" while making The Argentine, and he describes the project as a "very contemplative movie", shot chronologically.

"[14] Soderbergh decided to omit the post-revolution execution sentences of "suspected war criminals, traitors and informants" that Guevara reviewed at La Cabana Fortress because "there is no amount of accumulated barbarity that would have satisfied the people who hate him".

[20] IFC Films paid a low seven-figure sum to acquire all North American rights to Che after production had completed and released it on 12 December 2008 in New York City and Los Angeles in order to qualify it for the Academy Awards.

Del Toro remarked that the "legendary rebel" was still pertinent because "the things that he fought for in the late 1950s and mid 1960s are still relevant today", adding that "he did not hide behind curtains ... he stood up for the forgotten ones".

[51] Todd McCarthy was more mixed in his reaction to the film in its present form, describing it as "too big a roll of the dice to pass off as an experiment, as it's got to meet high standards both commercially and artistically.

[49] Glenn Kenny wrote, "Che benefits greatly from certain Soderberghian qualities that don't always serve his other films well, e.g., detachment, formalism, and intellectual curiosity".

[53] Peter Bradshaw, in his review for The Guardian, wrote, "Perhaps it will even come to be seen as this director's flawed masterpiece: enthralling but structurally fractured—the second half is much clearer and more sure-footed than the first—and at times frustratingly reticent, unwilling to attempt any insight into Che's interior world".

[54] In his less favorable review for Esquire, Stephen Garrett criticized the film for failing to show Guevara's negative aspects, "the absence of darker, more contradictory revelations of his nature leaves Che bereft of complexity.

This included adding a moment of Guevara and Fidel Castro shaking hands, tweaking a few transitions, and tacking on an overture and entr'acte to the limited "road show" version.

[58] However, Dargis notes that "Mr. Soderbergh cagily evades Che's ugly side, notably his increasing commitment to violence and seemingly endless war, but the movie is without question political—even if it emphasizes romantic adventure over realpolitik—because, like all films, it is predicated on getting, spending and making money".

[59] In his review for UGO, Keith Uhlich wrote, "The best to say about Del Toro's Cannes-honored performance is that it's exhausting—all exterior, no soul, like watching an android run a gauntlet [sic] (one that includes grueling physical exertions, tendentious political speechifying, and risible Matt Damon cameos)".

[60] Slant Magazine gave Che two-and-a-half stars out of four and wrote, "The problem is that, despite his desire to sidestep Hollywood bio-hooey, the director is unable to turn his chilly stance into an ideological perspective, like Roberto Rossellini did in his demythologized portraits of Louis XIV, Garibaldi and Pascal".

[61] In his review for Salon.com magazine, Andrew O'Hehir wrote, "What Soderbergh has sought to capture here is a grand process of birth and extinguishment, one that produced a complicated legacy in which John McCain, Barack Obama, and Raúl Castro are still enmeshed.

[64] When asked days later about the incident, Del Toro remarked that the ability to speak out was "part of what makes America great" while adding "I find it a little weird that they were protesting without having seen the film, but that's another matter".

[70] On 3 March 2009, Venezuelan President Hugo Chávez, himself a socialist and admirer of Che Guevara, greeted Del Toro and co-star Bichir at the Presidential Palace in Caracas.

The website's critical consensus states, "Though lengthy and at times plodding, Soderbergh's vision and Benicio Del Toro's understated performance ensure that Che always fascinates.

The website's critical consensus states, "The second part of Soderbergh's biopic is a dark, hypnotic and sometimes frustrating portrait of a warrior in decline, with a terrific central performance from Del Toro.".

[78] Hoberman compared Soderbergh's directing style and "non-personalized" historical approach on the film to Otto Preminger's observational use of the moving camera, or one of Roberto Rossellini's "serene" documentaries.

[78] Armond White, in his review for the New York Press, wrote, "Out-perversing Gus Van Sant's Milk, Soderbergh makes a four-hour-plus biopic about a historical figure without providing a glimmer of charm or narrative coherence".

[80] Sheri Linden, in her review for the Los Angeles Times, wrote, "in this flawed work of austere beauty, the logistics of war and the language of revolution give way to something greater, a struggle that may be defined by politics but can't be contained by it".

[97] On 31 July 2009, Del Toro was awarded the inaugural Tomas Gutierrez Alea prize at a Havana ceremony attended by U.S. actors Robert Duvall, James Caan, and Bill Murray.