Television critics reacted very positively to "Road to the Multiverse", calling the storyline "the best of the early episodes we've seen on the series." In a simultaneous review of the episodes of The Simpsons and American Dad! that preceded and followed the episode respectively and The Cleveland Show pilot, The A.V. Club's Todd VanDerWerff commented that he felt "essentially predisposed to like" the episode, adding that he enjoyed the entire theme of the show, in addition the fact that it was more than just science fiction. In the conclusion of his review VanDerWerff called the episode a "solid start to the eighth season" and rated it as a B+, the best rating between The Simpsons episode "Homer the Whopper", the American Dad! episode "In Country...Club" and The Cleveland Show's series premiere. Ahsan Haque of IGN gave the episode a 9.6 out of 10, saying that the episode featured "plenty of memorable lines, some truly stunning animation [...] and a relentless non-stop barrage of witty jokes." In a subsequent review in January 2010 of "Stewie and Brian's Greatest Adventures", Haque called the episode "creative, visually impressive, and features some of the best random gags we've seen on the show in a long time." Television critic Alex Rocha of TV Guide also found the episode to have "great laughs," saying that the show is "definitely off to a great start" to a new season. The director of "Road to the Multiverse", Greg Colton, was awarded the Primetime Emmy Award for Outstanding Individual Achievement in Animation, for storyboarding the episode, on August 21, 2010, at the 62nd Primetime Emmy Awards's Creative Arts Awards.
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