Robert Kaluza, 62, and Donald Vidrine, 65, were the highest ranking supervisors onboard the Deepwater Horizon rig at the time of the explosion that killed 11 people and caused one of the worst oil spills in history.
Prosecutors told a New Orleans court the on-site managers ignored "glaring red flags that the well was not secure" and failed to take "appropriate action" to prevent the blowout.
Defence lawyers said the pair were being unfairly targeted.
"The problem with this is that Congress and others demand human flesh to pay for terrible casualties like this," Mr Kaluza's lawyer, Bob Habans, told reporters outside the court.
"This time they chose Donald Vidrine and Bob Kaluza as the scapegoats for this prosecution."
The men face up to 10 years in prison on each of the 11 counts of manslaughter and eight years in prison on each of the 11 counts of involuntary manslaughter.
Earlier, the Environmental Protection Agency (EPA) announced BP had been temporarily suspended from new contracts with the US government.
The ban will see the company blocked from bidding for contracts until it shows it meets US government business standards.
It does not affect existing contracts and it is unclear how long it will last.
The suspension comes after BP was hit with a record $US4.5 billion fine over the Gulf of Mexico oil spill.
In announcing the ban, the EPA cited what it called BP's "lack of business integrity" over its handling of the Deepwater Horizon disaster.
The company has pleaded guilty to 14 criminal charges over the accident.
BP says it hopes to have the ban lifted as quickly as possible, and has been working with the EPA to prove it can meet federal standards.
"As BP's submissions to the EPA have made clear, the company has made significant enhancements since the accident," BP said in a statement.
"In the two-and-a-half years since the Deepwater Horizon accident, the US government has granted BP more than 50 new leases in the Gulf of Mexico, where the company has been drilling safely since the government moratorium was lifted."
But BP's woes look to be far from over.
It must still resolve a civil case on environmental fines that could amount to as much as $US18 billion if gross negligence is found.
It also remains on the hook for economic damages, including the cost of environmental rehabilitation.