On 17 April 2010 the Hispania Racing team announced that Yamamoto would become the test and reserve driver for the team, and that he would drive the car in free practice sessions over the course of the 2010 season, helping Hispania develop their car. He took part in his first practice session for the team at the where he set the slowest lap time of the session. On 8 July 2010 HRT team principal Colin Kolles announced that Yamamoto was to replace Bruno Senna for the , where he qualified 24th and last, he went on to finish 20th and last, just behind his team-mate Karun Chandhok. Yamamoto replaced Chandhok at the , where he retired after 19 laps with an engine problem. He kept this seat for the , in which he was lapped by his team-mate Senna. At the , Yamamoto accelerated from the pits as a mechanic was fixing the radio connection to his helmet. His rear wing struck the mechanic resulting in him being taken to hospital where he stayed for 10 days before being discharged and returning home to Germany. He was replaced at the by test driver Christian Klien after reportedly suffering food poisoning. He returned at the following race in Japan, finishing in 16th place, albeit last of the 16 cars to make the flag. He bettered this result by coming 15th in Korea, but was again replaced by Klien for the final two races in Brazil and Abu Dhabi.