Jeffery Woodke, who works for a local NGO called JEMED and has lived in Niger since 1992, was taken from his home in the town of Abalak at around 2000 GMT by a group of armed men in a Toyota Hilux pickup truck, the statement said.
"These criminals are now heading towards Mali. Our forces are on their trail," said interior minister Mohamed Bazoum.
Residents reported hearing gunfire near the aid worker's house late on Friday. The town mayor, Ahmed Dilo, told Reuters that gunmen first came on a motorbike to kill the guard before the truck came to take Woodke away.
The interior minister said one national guard stationed at the house was also killed.
Kidnappings of foreigners in Niger are rarer than in neighbouring Mali, where Islamist militants are active and often seize hostages for ransom or political capital.
The militants and allied criminal gangs have long exploited the largely unpoliced Sahara and attacks have increased this year as security worsens in Mali.
No US citizen has been kidnapped in Niger before, although in 2009 suspected Islamists attempted to abduct US embassy personnel from a hotel in the town of Tahoua.
A US embassy spokeswoman said there was an investigation into the incident but could not confirm any additional details. The US State Department said it was aware of reports but declined to comment citing US privacy laws.
Jeffery Woodke was taken from his home in the town of Abalak at around 2000 GMT
Gunmen raided the house of a US aid worker in central Niger on Friday night, killing his guard and housekeeper before driving him across the desert towards Mali, the interior ministry said in a statement on Saturday.
