Authorities have not released a motive or any information about what led up to the gunfire.
According to police, the shooting occurred around 2:30 p.m. on North Adams Street, near West 7th Street, where first responders were seen treating multiple victims.
Two men, 19-year-old Ryan Evans and 21-year-old Wahkee Tabron, both of Newark, were taken to the hospital and later died.
A 36-year-old man and a 37-year-old woman were taken to the hospital in critical condition.
The violence unfolded just outside the home of Terrielle Jordan, who said she initially mistook the sounds for construction.
Wilmington shooting leaves 2 dead, 2 critically injured
"I've never been so close up on something that happened like that," she said.
Jordan said a bullet struck her front door, and the incident left her thinking about how easily she or her children could have been harmed.
"I could've been walking to the corner store and been caught in the crossfire. My kids could've been without a mom, or I could've just genuinely opened my door to see what's going on," she said. "So I just think that everybody should be a little more considerate of other people that's around them."
Jordan added that this is the third shooting nearby since moving into the neighborhood a few months ago.
"I was debating on if I wanted to stay another year, but I think I'm probably going to move. This is too much," she said.
Chopper 6 video of shooting scene on N. Adams Street in Wilmington, Delaware
Another neighbor, who has lived in the area for nearly a decade, suggested the shooting may have been drug-related, though police have not confirmed any motive.
"It's commonplace here, it's common," said Rick Johnson. "They need to come here and clean this up. That's what they need to do. They know what's going on."
It remains unclear whether any of the victims may have been innocent bystanders. The investigation is ongoing.
Authorities are urging anyone with information to contact Wilmington Police or Delaware Crime Stoppers.