BALTIMORE — After two prosecutions without a conviction since the fatal arrest of Freddie Gray, opening arguments are set to begin Thursday in the trial of Caesar R. Goodson Jr., the only officer charged with murder in connection with the death and the driver of the police wagon in which Mr. Gray suffered the spinal injury that killed him.

The combination of the two unsuccessful prosecutions and the murder charge has raised the stakes substantially in the trial of the third of six officers charged in the death of Mr. Gray, 25, a black man whose death spurred riots, looting and arson.

“These are the most serious charges,” said Warren S. Alperstein, a defense lawyer here who has represented police officers and has been closely following the cases but is not directly involved in them. “This is, arguably, the make-or-break case for the state. It would be a devastating blow if the state was unable to secure a conviction.”

The trial comes as prosecutors aim to shift the narrative away from the mistrial of one officer involved in the case and, just over two weeks ago, another one’s acquittal on all charges.