Larry Gopnik, a Midwestern physics teacher, watches his life unravel over multiple sudden incidents. Though seeking meaning and answers amidst his turmoils, he seems to keep sinking.

Larry Gopnik (Michael Stuhlbarg) is a physics professor at a 1960s university, but his life is coming apart at the seams. His wife (Sari Lennick) is leaving him, his jobless brother (Richard Kind) has moved in, and someone is trying to sabotage his chances for tenure. Larry seeks advice from three different rabbis, but whether anyone can help him overcome his many afflictions remains to be seen.