The annual list is calculated by weighing a star's pay cheque against the money generated by his or her ticket sales at the box office, and thanks to box office bombs like Imagine That, A Thousand Words, and Meet Dave, Murphy only averaged an estimated return of $2.30 (£1.44) for every $1 (£0.63) earned.
The poll marks a step in the wrong direction for Murphy, who was second on last year's Forbes list behind Drew Barrymore. She fell out of the top 10 this year due to the fact she took time away from making movies to become a mum.
Faring slightly better is Katherine Heigl in second place - her most recent films, One for the Money, New Year's Eve and Life as We Know It, returned $3.40 (£2.10) for every dollar.
Oscar winners Reese Witherspoon and Sandra Bullock are surprising entries at three and four, respectively, while funnyman Jack Black rounds out the top five.