Husel pleaded not guilty and his lawyer said the doctor did not intend to kill anyone.
If convicted, Husel could face 15 years to life in prison on each count. His bond was set at $1 million.
The charges came following a six month investigation by Columbus police.
Mount Carmel Health System said an internal investigation found evidence that Husel ordered “significantly excessive” doses of painkillers for 35 patients over the past five years. All 35 died, though the hospital said for six of them the excessive doses went beyond providing comfort but were likely not the cause of death.
“Mount Carmel has made and will continue to implement meaningful changes throughout our system to ensure events like these never happen again,” the hospital said in a written statement Wednesday.
O’Brien said investigators focused the 25 patients for whom Husel ordered more than 500 micrograms of fentanyl.
Related: Columbus hospital deaths put spotlight on patient safety
Mount Carmel and Husel are facing multiple civil lawsuits over the patient deaths, although some have recently been settled out of court.
The State Medical Board of Ohio suspended Husel’s medical license in February.
The accusations against Husel are rare. Ohio last saw a case of the same scale three decades ago when hospital orderly Donald Harvey admitted to poisoning to death 24 patients at Cincinnati's Drake Hospital in 1986 and 1987. Harvey was beaten to death in a state prison in March 2017.
Information from the Associated Press is included in this report.