Mr Honken’s death sentence on Friday followed the executions of Daniel Lewis Lee and Wesley Ira Purkey.
Lawyers, who were hoping for a last-minute reprieve, said Mr Honken was “redeemed” and had repented for his crimes.
“There was no reason for the government to kill him, in haste or at all. In any case, they failed. The Dustin Honken they wanted to kill is long gone,” lawyer Shawn Nolan told the Associated Press.
A meth kingpin convicted of killing five people has become the third person this week to be executed by the US government.
Former Iowa chemistry student Dustin Honken, 52, was pronounced dead by lethal injection at 4.36 pm, according to the Bureau of Prisons.
“The man they killed today was a human being, who could have spent the rest of his days helping others and further redeeming himself. May he rest in peace.”
Mr Honken was pronounced dead about 30 minutes after receiving the lethal injection. His last words were “Holy Mary, mother of God, pray for me”.
Justice Department spokesperson Kerri Kupec said in a statement that a just punishment has been carried out.
“Nearly three decades after Honken coldly ended the lives of five people, including two young girls, all in an effort to protect himself and his criminal enterprise, he has finally faced justice,” Ms Kupec said.
Mr Honken was sentenced to death in 2004, 11 years after he kidnapped and killed Lori Duncan and her two daughters, Kandi, 10, and Amber, 6, as well as Ms Duncan’s boyfriend Greg Nicholson, a government informant who testified against him.
He also murdered Terry DeGeus, who he through might testify against him in federal drug trafficking charges.
Mr Honken, who had begun cooking meth after studying chemistry at an Iowa community college, was arrested after one of his dealers, Mr Nicholson, turned on him to investigators.
He was the third person executed this week after death sentences were carried out against Mr Lee on Tuesday and Mr Purkey on Thursday.
Mr Lee was executed for murdering an Arkansas family in the 1990s in an attempt to create a white nation in the Pacific Northwest, while Mr Purkey was executed for kidnapping, killing, and dismembering a six-year-old girl.
Together, they bring the total number of executions to 10 so far in 2020.