Arnautovic missed West Ham's last two games after he was tempted to accept a lucrative offer from a Chinese club. On Friday, he said he was staying at the London club and signed a new contract.
He was recalled by West Ham manager Manuel Pellegrini but didn't finish the match after hobbling off in the 77th minute with a leg injury following a tackle from Wolves midfielder Ruben Neves. He was wearing a protective boot as he left the stadium.
Raul Jimenez's late double inspired Wolves to an ultimately comfortable victory after West Ham goalkeeper Lukasz Fabianski threatened to frustrate the hosts.
Romain Saiss opened the scoring with a header from a corner in the 66th, before Jimenez took his tally to 12 goals for the season with strikes in the 80th and 86th minutes.
Wolves climbed to seventh place in the Premier League. West Ham lost three days after exiting the FA Cup at the hands of third-tier struggler AFC Wimbledon.