Whether it's his superior wrestling, athletic abilities, physical strength or a combination of all three, Lesnar has proved to be too much for heavyweights to handle. Until now.
For the first time in his brief mixed martial arts career, Lesnar will enter the Octagon to face a man who might very well be his physical equal. He will meet interim heavyweight titleholder Shane Carwin on Saturday night at UFC 116 in Las Vegas.
Unlike his predecessors, the 6-foot-2 Carwin has enough size, strength, athletic ability and wrestling skills to dethrone Lesnar. Toss in Carwin's tremendous punching power and it's not difficult to envision Lesnar sprawled on the canvas at the end of the night.
If Carwin touches Lesnar on the chin hard enough, this fight could be over in a flash. Carwin has the power to finish any man, even an imposing figure like Lesnar.
"If I touch anybody with my hands, I can knock them out," Carwin said recently during a conference call.
Carwin's hands are quickly becoming legendary. His mitts are considered the largest and most powerful in mixed martial arts.
Every one of Carwin's 12 professional opponents has tasted his power; not one has made it to the second round. Lesnar does not intend to be victim No. 13.
"Shane poses some different threats that I haven't had to face before, the size and strength and the wrestling," said Lesnar, who is 4-1-0. "[Shane's] got knockout power, so we train to avoid it.
"Obviously there are things that we want to do, and there's things that we want to avoid."
One thing Lesnar could not avoid was his long layoff. This will be Lesnar's first bout since July 2009, when he exacted revenge on Mir.
That Lesnar is fighting again is an example of his determination. He was scheduled to face Carwin in November 2009, but pulled out of the fight.
Shortly thereafter it was revealed that Lesnar was battling mononucleosis. Then it was later discovered that Lesnar had a more serious case of diverticulitis.
No longer was Lesnar battling for his mixed martial arts career, but for his life. But Lesnar is a fighter, a very good one, and he survived.
While recovering, Lesnar had time to reflect. He got a second chance at life, and is enjoying it more than ever.
The change could not have come at a better time. Lesnar has developed a new appreciation for mixed martial arts and entered this training camp with fresh determination.
"I went back to the drawing board on life when I was sick," Lesnar said. "I had to focus on a lot of different things. I mean my life first and my family and all these other things.
"When I finally got down and decided that I could fight and continue this legacy, I thought, 'You know what, I've got to make some changes. I want to get better. When I come back I want to be in greater shape. I want to be a better fighter.'"
And on fight night, Lesnar will be a better fighter than the one who manhandled Mir, Heath Herring and Randy Couture. He is more than just a powerful wrestler looking to take opponents to the ground and pound them.
Lesnar has been working diligently to improve his standup skills. He has added boxing trainer Peter Welch to his team. Welch has helped UFC lightweight contender Kenny Florian take his boxing skills to a higher level.
With Welch in his corner, Lesnar is becoming less predictable. If given the opportunity, he will shoot for a takedown. Unlike in past fights, however, expect to see Lesnar deliver more jabs.
He also is expected to keep his hands held high, which is important. Lesnar must keep his hands up and protect his chin at every moment against Carwin or he might not see Round 2.
In addition, Lesnar has added Jacksonville Jaguars strength and conditioning coach Luke Richesson to his team. For this fight, Lesnar has left no stones unturned.
The conditioning program has paid off. Lesnar, who stands 6-foot-3, no longer walks around at more than 300 pounds. He claims to already be at the 265-pound heavyweight limit.
"When I pulled the pin on this fight last October, I really regrouped and kind of rejuvenated myself," Lesnar said. "I took a new approach on it as far as training and everything.
"It's been very refreshing and I've really came leaps and bounds. It's been a great thing. I'm excited to fight."
But Lesnar won't be the only man inside the Octagon at UFC 116 filled with excitement. Carwin is eager to get his hands on the champ.
A few days ago, Carwin announced that he was only 10 pounds over the weight limit -- which is normal for him. He claims to be in great physical and mental condition. It's similar to the way he felt days before stopping Mir at UFC 111 in March.
If all goes according to plan, Carwin says that judges won't be necessary Saturday night. He is looking to finish this one quickly.
"I've prepared in all areas," Carwin said. "I'm just ready to get in there and fight and do what I love to do. This is fun for me.
"I like to fight. It's what I enjoy doing, this is what I love to do. I'm passionate about it.
"I'm not looking to eke out decisions or anything. I want to get in there and I want to fight. That's just my mentality, my attitude."
Franklin McNeil is a contributing mixed martial arts/boxing writer for ESPN.com. He also appears regularly on "MMA Live," which now airs on ESPN2.