Crawford, on home turf in Lincoln, Nebraska, knocked out Julius Indongo in the third-round to become only the second male boxer to unify the four major organisation titles since Bernard Hopkins beat Oscar De La Hoya at middleweight in 2004.
Crawford (32-0) had already knocked Indongo to the canvas once in the second round, but sealed victory in the third with a huge left hook to the body.
Crawford came into the fight with the WBC and WBO belts, while Namibian Indongo (22-1) held the WBA and IBF titles.
Speaking after the fight, a jubilant Crawford said: "This is a dream come true. Thank you Nebraska, thank you the US - I did this for all of us.
"Belts matter and I am the only world champion at 140lbs - it is a big deal to me. We have been practising body shots all camp and everything we worked on in camp came out today.
"Now I want to rest up and enjoy this moment. My managers and coaches will see what is next for me."
Earlier in the evening, Whyte stopped Malcolm Tann in three rounds.
Whyte (21-1) was fighting for the first time since his victory over Dereck Chisora in December.
He dominated the bout against Tann, using a right-left combination to drop the 38-year-old for a fourth and final time.
The 29-year-old Whyte is hoping the victory will now set him up for a fight against WBC world heavyweight champion Deontay Wilder.
"I'm a natural body puncher and try to hurt these guys to the body,” Whyte told ESPN.
"Against Deontay Wilder, imagine those shots? With his thin, lean body he’d fall after three or four rounds. I believe in my power. If I land I can knock any of these heavyweights out."
