The pair collide at the AT&T Stadium in Texas and the WBA, WBC and IBF belts will be on the line on April 16.
Spence unified the division with victory over Shawn Porter and most recently defeated Danny Garcia in December 2020 to retain his WBC and IBF straps.
Meanwhile, Ugas delivered a shock victory over 42-year-old Manny Pacquiao last summer to win the WBA title.
Atlas believes Spence won't give Ugas the same chances to land punches like Pacquiao did.
"Ugas won the fight, but it was close. Pacquiao made it closer than a lot of people want to admit," said Teddy Atlas on The Fight. "The reason it was close is because Pacquiao outworked him.
"I don't think he's going to outwork Spence, so that means he's going to have to do what he did with Pacquiao. He's going to have to land the cleaner, harder punches to affect him," said Atlas about Ugas.
Talking about Spence's credentials, Atlas added: "First of all, Spence has a really good chin," said Atlas. "A counter puncher [like Ugas] needs to be in a certain environment to be at their best. The environment he had with Pacquiao was the right environment.
"A counter puncher needs his opponent to be aggressive and recklessly aggressive sometimes. That's Pacquiao. He got away with it because Pacquiao was so fast, but as he got older, he was a little slower and he paid a price in the Ugas fight in getting hit with right hands. Right hands are the southpaw killer," said Atlas.
Spence inflicted the first defeat on Mikey Garcia's career in 2019 and won his first world title against Kell Brook in his hometown of Sheffield, England. The American delivered an 11th-round stoppage.
While Atlas expects Spence to unify the division and move one title away from becoming undisputed champion, he has predicted it will go the distance.
"Ugas had that and he was able to time Pacquiao all night long with the right hand," said Atlas. "Again, Pacquiao gave him what he needed by being aggressive. He's not going to get that help from Spence.
"As big and as strong Spence is, he's cautiously aggressive. Yeah, he's aggressive, but behind the jab. Everyone thought Mikey Garcia would have a chance against the bigger Spence by countering him. No, he didn't. Do you know why? Because Spence out-jabbed him.
"When a guy is using his jab from the right distance, it's very hard for a counter puncher to be on his A-game because he needs something to counter.
"When you're jabbing and staying at range and controlling with a jab, you're not giving a counter puncher anything to counter. That's how I see this fight. Spence will not give Ugas what Pacquiao gave him. A target just coming in where he was able to time him coming in with counters.
"He's [Spence] going to hit him with jabs. He's going to come in behind that jab, that southpaw jab, and it's going to take a lot of Ugas's game away.
"I'm picking Spence because of what I just said. I think it'll go the distance. Another thing about Spence that bodes well for him. Spence is good defensively, Spence is a good body puncher.
"You can break down a man's defence a little when you go to the body. I'm going with Spence," said Atlas.
A potential clash between Spence and Terence Crawford could happen towards the end of the year, and if it does, it'll be the biggest fight of the year.