The shutdown began Saturday night as work continued on the construction project near Penn's Landing.
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The latest closure was the second one associated with Philadelphia's CAP project.
On Sunday night, officials said the demolition work that necessitated the shutdown was complete and that all of the existing covered sections on the highway were down.
Ahead of Monday morning's reopening, crews were working on cleanup as debris needed to be cleared from the southbound lanes of the highway.
Meanwhile, PennDOT wants drivers to know the Market Street ramp to I-95 South will be closed from Feb. 19 to March 11.
For the latest road conditions in your area, visit 6abc.com/Traffic.
Construction continues on I-95 CAP project
The weekend closure was similar to what drivers experienced when the northbound lanes were closed a few weeks ago, but crews say this process was trickier for them to tackle.
The work done during the northbound closure earlier this month was completed in about 30 hours.
However, PennDOT officials previously told Action News the southbound side was trickier because after the demolition, there wasn't much space on the southbound side to move the debris.
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RELATED: New renderings, timeline released for Park at Penn's Landing
New renderings, timeline released for Park at Penn's Landing
PennDOT says these weekend closures accelerate the demolition process on I-95 by about four to five months. The goal of the $329 million plan is to replace and expand the existing covered area over I-95 between Chestnut and Walnut streets with a park that is nearly 12 acres. It is expected to be completed in 2028.
Residents react to I-95 closure
Sunday was the last day of the second scheduled road closure for parts of I-95 South. Residents across Philadelphia say they are relieved, as the weekend travel was difficult to navigate.
"I just had to zig-zag and go to 2nd Street instead of Delaware because I didn't want to follow the herd," noted Chris McDaniel from Queens Village.
Some people told Action News they avoided driving altogether to stay away from the construction on I-95.
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"It's been a pain, I actually Uber and because of the roads I decided not to work because I don't feel like dealing with the headache," said McDaniel.
"Nightmare traffic, that's what impacts us the most. Our bedrooms are right off Columbus Boulevard, it's a nightmare really," said Angela Hauad from Queens Village.
Hauad added that she was nervous the project would not go well for the city in the long run.
"I think it's gonna backfire, for the city. It's gonna go wrong, be a total mess, and a lot of people are gonna be aggravated," she said.
Others are hopeful the road closures will be worth the headache.
"The sooner they fix this the better. I know they're building a park, so build that park! Let's do it, let's go," said McDaniel.
For the latest road conditions in your area, visit 6abc.com/Traffic.