The explosion at around 5am local time (09:00 GMT) at the Dar Al Farooq Islamic Center in Bloomington, Minnesota, caused damage but did not cause any casualties.
Worshippers had been preparing for the dawn prayer when the attack happened.
There were between 15 and 20 people inside the building at the time, according to Star Tribune, a local newspaper.
The Federal Bureau of Investigation (FBI) has sent agents to track down who was behind the attack, which it says was caused by an "improvised explosive device".
The mosque, like many others in the US, received threats of attack prior to the bombing.
For many, the response, or lack of it, revealed a double standard.
Some questioned why US President Donald Trump failed to respond to what they described as a "terrorist attack" targeting Muslims.
Mark Follman, an editor at the progressive-leaning Mother Jones magazine, said Trump's silence was due to the target of the attack.
"In normal times, the bombing of a house of worship with an IED would not go unacknowledged by the president of the United States," he continued, after posting a list of previous attacks committed by far-right attackers that Trump had also not responded to.
Marty Parrish asked: "Did I miss Trump's statement of concern for the victims of this bombing and members of the Mosque?" Adding: "Does he care?"
But Trump was not the sole target of anger, with some railing against the purported lack of media coverage.
Some US-based outlets did publish stories on the attack, but that did not assuage the anger.
A Twitter user named Brown Saraah wrote: "Someone bombed a mosque in Minnesota recently. You probably didn't hear about this because mainstream media likes to demonize Muslims."
Activist Simran Jeet Singh accused the media of avoiding the term "terrorism".
"Are you kidding with this headline right now? Can you not [call] it terrorism because Muslims were the targets? Why the double-standard?" He said, in response to a New York Times article, which used the term "explosion" to describe the attack.
As with other recent attacks, well-wishers were quick to make donations to the mosque to help it repair damage to the mosque.
By the time of publishing, hundreds of people had donated a total of $12,000 to repair the damage on two fundraising pages.
The latest attack comes amid rising Islamophobic sentiment.
The Council on American-Islamic Relations (CAIR) has said that discrimination against Muslims swelled during the 2016 election campaign and has continued to rise following Trump's election victory.
The US president campaigned on a platform that promised a blanket ban on Muslims entering the country, as he vowed to closely monitor mosques.